This PTEN/ARID4B/PI3K signalling axis identifies a novel player in the PTEN mediated suppression of the PI3K pathway and provides a new opportunity to design novel therapeutics to target this axis to promote the tumour suppressive functions of PTEN.

In one of these studies, Baker et al. reported that Notch1 can mediate transcriptional suppression of PTEN, resulting in the derepression of PI3K signalling and development of trastuzumab resistance 91.

This study was the first to link the Ras-MAPK and PI3K pathways through Notch1 transcriptional suppression of PTEN 91.

It was reported that PTEN could dephosphorylate PGK1, a glycolytic enzyme and protein kinase with a tumorigenic role in glioblastoma 99.

Dephosphorylation of PGK1 by PTEN was found to inhibit its activity, downstream glycolytic functions, and glioblastoma cell proliferation 99, thereby presenting another mechanism in which PTEN functions as a tumour suppressor.

Newer studies add to this small body of data, including an intriguing study where a novel PTEN/ARID4B/PI3K pathway in which PTEN inhibits the expression of ARID4B was characterised.

PTEN inhibits ARID4B expression and thus prevents the transcriptional activation of ARID4B transcriptional targets PIK3CA and PIK3R2 (PI3K subunits) 79.

Furthermore, nuclear PTEN directly interacted with and inhibited RNA polymerase II (RNAPII)-mediated transcription, where it was involved in direct downregulation of critical transcriptional control genes including AFF4 and POL2RA 80.

Colocalisation of PTEN and PTENalpha promoted the function of PINK1, a mitochondrial-target kinase, and subsequently promoted energy production 105.

It is known that AKT signaling plays a critical role in the regulation of pre-mRNA splicing 77 and PTEN has been shown to modulate G6PD pre-mRNA splicing in an AKT independent manner 78.

Numb inhibits Notch1, leading to the downregulation of RBP-Jkappa 94, which upregulates PTEN and anti-EMT effectors, leading to the downregulation of p-FAK and pro EMT effectors 94.

IL-1beta secretion was not affected by treatment with the NLRP3 inhibitor glyburide XREF_BIBR or parthenolide, which has also been shown to inhibit NLRP3 XREF_BIBR.

Glyburide and parthenolide both inhibited NLRP3 activation by LPS and ATP (data not shown).

XREF_BIBR have shown that parthenolide directly inhibits caspase-1 by alkylation of certain cysteine residues.

Nonetheless, transcripts of genes associated with IL-17 production, such as IL17F, RORC, IL23R, and CCR6, were significantly decreased in CD8 + CD103 + CD49a + relative to CD8 + CD103 + CD49a - Trm cells, whereas transcripts for IFN-gamma were elevated (XREF_FIG D-E).

Nonetheless, transcripts of genes associated with IL-17 production, such as IL17F, RORC, IL23R, and CCR6, were significantly decreased in CD8 + CD103 + CD49a + relative to CD8 + CD103 + CD49a - Trm cells, whereas transcripts for IFN-gamma were elevated (XREF_FIG D-E).

CD103 binds E-cadherin, which is highly expressed on epithelia, whereas CD69 antagonizes sphingosine 1-phosphate receptor 1 (S1PR1)-mediated egress from tissues.

Nonetheless, transcripts of genes associated with IL-17 production, such as IL17F, RORC, IL23R, and CCR6, were significantly decreased in CD8 + CD103 + CD49a + relative to CD8 + CD103 + CD49a - Trm cells, whereas transcripts for IFN-gamma were elevated (XREF_FIG D-E).

Nonetheless, transcripts of genes associated with IL-17 production, such as IL17F, RORC, IL23R, and CCR6, were significantly decreased in CD8 + CD103 + CD49a + relative to CD8 + CD103 + CD49a - Trm cells, whereas transcripts for IFN-gamma were elevated (XREF_FIG D-E).

Nonetheless, transcripts of genes associated with IL-17 production, such as IL17F, RORC, IL23R, and CCR6, were significantly decreased in CD8 + CD103 + CD49a + relative to CD8 + CD103 + CD49a - Trm cells, whereas transcripts for IFN-gamma were elevated (XREF_FIG D-E).

Nonetheless, transcripts of genes associated with IL-17 production, such as IL17F, RORC, IL23R, and CCR6, were significantly decreased in CD8 + CD103 + CD49a + relative to CD8 + CD103 + CD49a - Trm cells, whereas transcripts for IFN-gamma were elevated (XREF_FIG D-E).

Further validating transcriptional data, CXCR3 expression was higher on CD8 + CD103 + CD49a + Trm cells, whereas IL-23R and CCR6 were preferentially expressed by CD8 + CD103 + CD49a - Trm cells (XREF_FIG G).

Further validating transcriptional data, CXCR3 expression was higher on CD8 + CD103 + CD49a + Trm cells, whereas IL-23R and CCR6 were preferentially expressed by CD8 + CD103 + CD49a - Trm cells (XREF_FIG G).

In addition, CD8 + CD49a + Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response.

In addition, CD8 + CD49a + Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response.

In addition, CD8 + CD49a + Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response.

Accordingly, IL-15-dependent expression of perforin and granzyme B was augmented by IL-6, but not other cytokine combinations tested (XREF_SUPPLEMENTARY C-S2E).

Rather, their cytotoxic capacity was primed through IL-2 and IL-15-mediated induction of perforin and granzyme B expression.

Rather, their cytotoxic capacity was primed through IL-2 and IL-15-mediated induction of perforin and granzyme B expression.

In addition, CD8 + CD49a + Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response.

In addition, CD8 + CD49a + Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response.

Moreover, IL-15 stimulation potentiated TCR dependent expression of IL-17 and IFN-gamma by epidermal CD8 + CD103 + CD49a - and IFN-gamma by CD8 + CD103 + CD49a + Trm cells, respectively (XREF_FIG D), substantiating effectual gamma chain receptor signaling in both subsets.

In addition, CD8 + CD49a + Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response.

Further validating transcriptional data, CXCR3 expression was higher on CD8 + CD103 + CD49a + Trm cells, whereas IL-23R and CCR6 were preferentially expressed by CD8 + CD103 + CD49a - Trm cells (XREF_FIG G).

Further validating transcriptional data, CXCR3 expression was higher on CD8 + CD103 + CD49a + Trm cells, whereas IL-23R and CCR6 were preferentially expressed by CD8 + CD103 + CD49a - Trm cells (XREF_FIG G).

Moreover, IL-15 stimulation potentiated TCR dependent expression of IL-17 and IFN-gamma by epidermal CD8 + CD103 + CD49a - and IFN-gamma by CD8 + CD103 + CD49a + Trm cells, respectively (XREF_FIG D), substantiating effectual gamma chain receptor signaling in both subsets.

In addition, CD8 + CD49a + Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response.

In addition, CD8 + CD49a + Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response.

In addition, CD8 + CD49a + Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response.

CD103 binds E-cadherin, which is highly expressed on epithelia, whereas CD69 antagonizes sphingosine 1-phosphate receptor 1 (S1PR1)-mediated egress from tissues.

Collagen IV mediated engagement of CD49a enhanced IFN-gamma production by CD8 + CD103 + CD49a + Trm cells, possibly through stabilizing IFNG transcripts.

Collagen IV mediated engagement of CD49a enhanced IFN-gamma production by CD8 + CD103 + CD49a + Trm cells, possibly through stabilizing IFNG transcripts.

Relative to the epidermal CD8 + CD103 + CD49a - Trm cells, dermal counterparts produced 3.5-fold less IL-17.

Collagen IV mediated engagement of CD49a enhanced IFN-gamma production by CD8 + CD103 + CD49a + Trm cells, possibly through stabilizing IFNG transcripts.

Relative to the epidermal CD8 + CD103 + CD49a - Trm cells, dermal counterparts produced 3.5-fold less IL-17.

Thus, CD49a expression delineated a dichotomy in Trm cell cytokine production, augmented by IL-15, with CD8 + CD103 + CD49a - and CD8 + CD103 + CD49a + Trm cells preferentially producing IL-17 and IFN-gamma, respectively.

Collagen IV mediated engagement of CD49a enhanced IFN-gamma production by CD8 + CD103 + CD49a + Trm cells, possibly through stabilizing IFNG transcripts.

Thus, CD49a expression delineated a dichotomy in Trm cell cytokine production, augmented by IL-15, with CD8 + CD103 + CD49a - and CD8 + CD103 + CD49a + Trm cells preferentially producing IL-17 and IFN-gamma, respectively.

In human skin epithelia, CD8 + CD49a + Trm cells produced interferon-gamma, whereas CD8 + CD49a - Trm cells produced interleukin-17 (IL-17).

Collagen IV mediated engagement of CD49a enhanced IFN-gamma production by CD8 + CD103 + CD49a + Trm cells, possibly through stabilizing IFNG transcripts.

IL-2 and IL-15 Induce Cytotoxic Effector Protein Expression in Epidermal CD8 + CD103 + CD49a + Trm Cells.

Conversely, CD8 + CD49a - Trm cells from psoriasis lesions predominantly generated IL-17 responses that promote local inflammation in this skin disease.

This functional dichotomy was evident in the comparison of distinct immune mediated skin diseases, with skin biopsies from vitiligo patients showing a predominance of cytotoxic CD8 + CD103 + CD49a + Trm cells while skin biopsies from psoriasis patients featured the accumulation of the IL-17 producing CD8 + CD103 + CD49a - counterparts.

Thus, CD49a expression delineated a dichotomy in Trm cell cytokine production, augmented by IL-15, with CD8 + CD103 + CD49a - and CD8 + CD103 + CD49a + Trm cells preferentially producing IL-17 and IFN-gamma, respectively.

Thus, CD49a expression delineated a dichotomy in Trm cell cytokine production, augmented by IL-15, with CD8 + CD103 + CD49a - and CD8 + CD103 + CD49a + Trm cells preferentially producing IL-17 and IFN-gamma, respectively.

Generally, IFN-gamma contributes to immunity toward intracellular infections while IL-17 provides anti-fungal defense and both of these cytokines initiate inflammatory keratinocyte responses.

In line withincreased CD49a frequencies, IFN-gamma producing Trm cells were enriched in vitiligo lesions (XREF_FIG G).

Nonetheless, transcripts of genes associated with IL-17 production, such as IL17F, RORC, IL23R, and CCR6, were significantly decreased in CD8 + CD103 + CD49a + relative to CD8 + CD103 + CD49a - Trm cells, whereas transcripts for IFN-gamma were elevated (XREF_FIG D-E).

Nonetheless, transcripts of genes associated with IL-17 production, such as IL17F, RORC, IL23R, and CCR6, were significantly decreased in CD8 + CD103 + CD49a + relative to CD8 + CD103 + CD49a - Trm cells, whereas transcripts for IFN-gamma were elevated (XREF_FIG D-E).

Nonetheless, transcripts of genes associated with IL-17 production, such as IL17F, RORC, IL23R, and CCR6, were significantly decreased in CD8 + CD103 + CD49a + relative to CD8 + CD103 + CD49a - Trm cells, whereas transcripts for IFN-gamma were elevated (XREF_FIG D-E).

TCR engagement using anti-CD3 antibodies also preferentially induced IFN-gamma by epidermal CD8 + CD103 + CD49a + Trm cells (XREF_FIG D).

Collagen IV mediated engagement of CD49a enhanced IFN-gamma production by CD8 + CD103 + CD49a + Trm cells, possibly through stabilizing IFNG transcripts.

Collagen IV mediated engagement of CD49a enhanced IFN-gamma production by CD8 + CD103 + CD49a + Trm cells, possibly through stabilizing IFNG transcripts.

Collagen IV mediated engagement of CD49a enhanced IFN-gamma production by CD8 + CD103 + CD49a + Trm cells, possibly through stabilizing IFNG transcripts.

Collagen IV mediated engagement of CD49a enhanced IFN-gamma production by CD8 + CD103 + CD49a + Trm cells, possibly through stabilizing IFNG transcripts.

Collagen IV mediated engagement of CD49a enhanced IFN-gamma production by CD8 + CD103 + CD49a + Trm cells, possibly through stabilizing IFNG transcripts.

TNF and IL-2 were abundantly produced by dermal and epidermal Trm cell subsets (XREF_FIG B and 6C).

TNF and IL-2 were abundantly produced by dermal and epidermal Trm cell subsets (XREF_FIG B and 6C).

TNF and IL-2 were abundantly produced by dermal and epidermal Trm cell subsets (XREF_FIG B and 6C).

Moreover, IL-17 or IFN-gamma production by distinct Trm cells subsets was generally maintained even in the context of the vigorous tissue inflammation.

Revealing functional specialization among epidermal Trm cells with respect to CD49a expression, CD8 + CD103 + CD49a - Trm cells preferentially produced IL-17, a cytokine required for control of bacterial and fungal infections.

Corroborating transcriptional profiles, CD8 + CD103 + CD49a - Trm cells produced IL-17 while CD8 + CD103 + CD49a + Trm cells excelled in IFN-gamma production upon stimulation with phorbol 12-myristate 13-acetate and ionomycin (XREF_FIG A-6C).

Thus, CD49a expression delineated a dichotomy in Trm cell cytokine production, augmented by IL-15, with CD8 + CD103 + CD49a - and CD8 + CD103 + CD49a + Trm cells preferentially producing IL-17 and IFN-gamma, respectively.

In human skin epithelia, CD8 + CD49a + Trm cells produced interferon-gamma, whereas CD8 + CD49a - Trm cells produced interleukin-17 (IL-17).

Here, we identify CD49a expression as a marker delineating a subpopulation ofCD8 + Trm cells in human skin that specifically localize to thebasal layer of epidermis, preferentially produce IFN-gamma, and display high cytotoxic capacity upon stimulation.

Moreover, IL-17 or IFN-gamma production by distinct Trm cells subsets was generally maintained even in the context of the vigorous tissue inflammation.

Thus, CD49a expression delineated a dichotomy in Trm cell cytokine production, augmented by IL-15, with CD8 + CD103 + CD49a - and CD8 + CD103 + CD49a + Trm cells preferentially producing IL-17 and IFN-gamma, respectively.

In human skin epithelia, CD8 + CD49a + Trm cells produced interferon-gamma, whereas CD8 + CD49a - Trm cells produced interleukin-17 (IL-17).

TNF and IL-2 were abundantly produced by dermal and epidermal Trm cell subsets (XREF_FIG B and 6C).

In summary, our findings establish that NLRP3 inflammasome activation drives the interactions of NLRP3 and ASC with F-actin as well as regulate the amount of cellular F-actin.

Accordingly, we observed that Ca 2+ / FliI dependent severing of F-actin suppresses F-actin/FliI/LRRFIP2-dependent NLRP3 inflammasome inhibition leading to increase IL-1beta production.

We further demonstrated that SPOP promoted the ubiquitination of LATS1 in cells (XREF_FIG j).

On the other hand, we observed that depletion of SPOP reduced cell invasion which can be rescued by additional depletion of LATS1 (XREF_FIG e, f).

These results suggest that SPOP downregulates cell invasion partly through modulating LATS1 protein abundance.

Notably, overexpression of SPOP rescued cell invasion inhibition induced by overexpression of LATS1 (XREF_FIG c, d).

Moreover, previous studies have shown that CKIota was involved in SRC-3 and ERG degradation mediated by SPOP [XREF_BIBR, XREF_BIBR].

Consistently, recent studies have identified that SPOP promoted SRC-3 and ERG degradation in a casein kinase Iota epsilon (CKIotaepsilon) -dependent and casein kinase Iota delta (CKIotadelta)-dependent manner [XREF_BIBR, XREF_BIBR].

CKIotadelta promotes the interaction and degradation of LATS1 by SPOP.

Cullin3 SPOP is the physiological E3 ubiquitin ligase for LATS1 and negatively regulates the protein stability of LATS1.

3.4 CKIotadelta promotes the interaction and degradation of LATS1 by SPOP.

In addition, we found that MTS1 kinase that phosphorylates LATS1 did not involve in SPOP mediated degradation of LATS1.

Given that the SPOP recognizable degron in LATS1 contains several putative CKI phosphorylation sites, we aimed to detect whether CKIota also involves in SPOP mediated degradation of LATS1.

Notably, deletion of degron1 (DeltaDeg1), and to a lesser extent of degron2 (DeltaDeg2), largely blocked SPOP mediated degradation of LATS1, whereas deletion of both degron1 and 2 (DeltaDeg1 +2) nearly abolished the LATS1 degradation of SPOP mediated (XREF_FIG b).

Moreover, either loss of MATH or BTB domain of SPOP prevented the degradation of LATS1.

Moreover, the half-life of LATS1 was markedly extended with depleting of endogenous SPOP protein, whereas overexpression of SPOP reduced the protein half-life of LATS1 (XREF_FIG d-g).

3.2 Cullin3 SPOP E3 ubiquitin ligase negatively regulates the protein stability of LATS1.

Moreover, previous studies have shown that CKIota was involved in SRC-3 and ERG degradation mediated by SPOP [XREF_BIBR, XREF_BIBR].

Consistently, recent studies have identified that SPOP promoted SRC-3 and ERG degradation in a casein kinase Iota epsilon (CKIotaepsilon) -dependent and casein kinase Iota delta (CKIotadelta)-dependent manner [XREF_BIBR, XREF_BIBR].

To this end, we observed that depletion of SPOP decreased cell proliferation in A498 kidney cancer cells (XREF_FIG a).

Notably, we observed that LATS1 interacted specifically with SPOP in cells (XREF_FIG f and Supplementary Fig. 1g and 1j).

In addition, PTEN and ERK governed the expression of beta-catenin, and mediated EMT in human cancer [XREF_BIBR, XREF_BIBR].

In keeping with a critical role of Cullin 3 in regulating LATS1 protein stability, depletion of Cullin 3 promoted the abundance of LATS1 (XREF_FIG c and Supplementary Fig. 1b).

Here we identified that the Cullin3 and SPOP E3 ligase mediates the abundance of LATS1 protein through promoting its ubiquitination and subsequent destruction.

Mechanistically, SPOP drove EMT and promoted cell invasion via enhancement of beta-catenin protein expression and its nuclear translocation and upregulation of TCF4 in ccRCC XREF_BIBR.

Thus, these studies indicate that SPOP mediated cell invasion in part via targeting PTEN and ERK, and activation of beta-catenin and TCF4 and subsequent upregulation of ZEB1.

On the other hand, SPOP could promote kidney cancer cell invasion in part via regulating LATS1.

Moreover, we found that overexpression of SPOP enhanced cell invasion (XREF_FIG c, d).

One recent study demonstrated that SPOP promoted renal cell carcinoma cell epithelial-mesenchymal transition (EMT) and enhanced cell invasion via activation of beta, catenin, and TCF4 complex [32].

Here we identified that the Cullin3 and SPOP E3 ligase mediates the abundance of LATS1 protein through promoting its ubiquitination and subsequent destruction.

Consistent with an important role for SPOP in modulating the stability of LATS1, we demonstrated that depletion of endogenous SPOP with several different small hairpin RNA (shRNA) markedly elevated the protein abundance of LATS1 in multiple cell lines (XREF_FIG a).

Therefore, our studies identified E3 ubiquitin ligase Cullin3 and SPOP mediated the stability of the tumour suppressor LATS1 through poly-ubiquitination and subsequent degradation of LATS1 in kidney cancer in a degron dependent manner.

It is worth noting that SPOP also targets PTEN, DUSP7, Daxx, and Gli2 in ccRCC XREF_BIBR, thereby suggesting that SPOP could exert its oncogenic function in part via LATS1 pathway.

SPOP promotes kidney cancer cell proliferation, invasion and regulates cell cycle in part via promoting the degradation of LATS1.

Together, these results suggest that SPOP promotes kidney cancer cell proliferation, invasion and regulates cell cycle in part via promoting the degradation of LATS1.

In line with this, we observed that overexpression of SPOP could promote cell proliferation partly through regulating cell cycle distribution in A498 cells and 786-O cells (XREF_FIG b).

On the other hand, overexpression of SPOP promoted cell proliferation in A498 cells and 786-O cells (XREF_FIG b).

We found that LATS1 interacted with Cullin3, and depletion of Cullin 3 upregulated the abundance of LATS1 largely via prolonging LATS1 protein half-life.

Mechanistically, SPOP specifically interacted with LATS1, and promoted the poly-ubiquitination and subsequent degradation of LATS1 in a degron dependent manner.

We found that LATS1 interacted with Cullin3, and depletion of Cullin 3 upregulated the abundance of LATS1 largely via prolonging LATS1 protein half-life.

Furthermore, SPOP also promoted kidney cancer cell invasion via degrading LATS1.

As such, over-expression of SPOP promoted cell proliferation partly through regulating cell cycle distribution in kidney cancer cells.

Here we report that TCF19 interacts with a non histone, well-known tumor suppressor protein 53 (p53) and co-regulates a wide array of metabolic genes.

Interestingly, we observed that TCF19 and p53 complexes either have CBP or HDAC1 to epigenetically program the expression of TIGAR and SCO2 genes depending on short-term high glucose or prolonged high glucose conditions.

Here we report that TCF19 interacts with a non histone, well-known tumor suppressor protein 53 (p53) and co-regulates a wide array of metabolic genes.

Interestingly, we observed that TCF19 and p53 complexes either have CBP or HDAC1 to epigenetically program the expression of TIGAR and SCO2 genes depending on short-term high glucose or prolonged high glucose conditions.

The low nutrient concentrations and high oxygen concentrations measured in these samples support the influence of the Polar Surface Water or the Polar Intermediate water from the EGC.

The knockdown of NLRP3 significantly reduces the proliferation, clonogenicity, invasion and migration in both Ishikawa and HEC-1A cells, while in contrast, NLRP3 overexpression enhances the proliferation, migration and invasion in both Ishikawa and HEC-1A cells and furthermore, increases caspase-1 activation and the release of IL-1beta in endometrial cancer cells.

Inhibition of NLRP3 suppresses the proliferation, migration and invasion, and promotes apoptosis in glioma cells, while in contrast, increased expression of NLRP3 significantly enhances the proliferation, migration and invasion as well as attenuating apoptosis in glioma cells (XREF_TABLE).

Similarly, NLRP3 expression levels are also correlated with the tumor size, lymph node metastatic status and IL-1beta expression in oral squamous cell carcinoma (OSCC), and downregulating NLRP3 expression markedly attenuates the proliferation, migration, and invasion of OSCC.

The knockdown of NLRP3 significantly reduces the proliferation, clonogenicity, invasion and migration in both Ishikawa and HEC-1A cells, while in contrast, NLRP3 overexpression enhances the proliferation, migration and invasion in both Ishikawa and HEC-1A cells and furthermore, increases caspase-1 activation and the release of IL-1beta in endometrial cancer cells.

Knockdown of NLRP3 suppresses UVB induced production of IL-1beta and attenuates other inflammatory mediators, such as IL-1alpha, IL-6, TNF-alpha and PGE 2.

The knockdown of NLRP3 significantly reduces the proliferation, clonogenicity, invasion and migration in both Ishikawa and HEC-1A cells, while in contrast, NLRP3 overexpression enhances the proliferation, migration and invasion in both Ishikawa and HEC-1A cells and furthermore, increases caspase-1 activation and the release of IL-1beta in endometrial cancer cells.

found that NLRP3 inhibits senescence and enables replicative immortality through regulating the Wnt and beta-catenin pathway via the thioredoxin interacting protein (TXNIP)/NLRP3 axis.

Consistently, knockdown of NLRP3 induces cell apoptosis in MCF-7 cells and decreases cell migration; nevertheless, in other cell-types, NLRP3 inflammasome may pharmacologically repress proliferation and metastasis of hepatic cell carcinoma (HCC) (XREF_TABLE).

The knockdown of NLRP3 significantly reduces the proliferation, clonogenicity, invasion and migration in both Ishikawa and HEC-1A cells, while in contrast, NLRP3 overexpression enhances the proliferation, migration and invasion in both Ishikawa and HEC-1A cells and furthermore, increases caspase-1 activation and the release of IL-1beta in endometrial cancer cells.

Inhibition of NLRP3 suppresses the proliferation, migration and invasion, and promotes apoptosis in glioma cells, while in contrast, increased expression of NLRP3 significantly enhances the proliferation, migration and invasion as well as attenuating apoptosis in glioma cells (XREF_TABLE).

found that NLRP3 overexpression inhibits cell proliferation and stimulates apoptosis in leukemic cells.

Similarly, NLRP3 expression levels are also correlated with the tumor size, lymph node metastatic status and IL-1beta expression in oral squamous cell carcinoma (OSCC), and downregulating NLRP3 expression markedly attenuates the proliferation, migration, and invasion of OSCC.

Consistently, knockdown of NLRP3 induces cell apoptosis in MCF-7 cells and decreases cell migration; nevertheless, in other cell-types, NLRP3 inflammasome may pharmacologically repress proliferation and metastasis of hepatic cell carcinoma (HCC) (XREF_TABLE).

NLRP3 inflammasome inactivation, driven by miR-223-3p, increases proliferation, promotes invasion and inhibits apoptosis in breast cancer cells.

The attenuation of the NLRP3 downstream pyroptosis pathway promotes apoptosis.

Similarly, activation of NLRP3 inflammasome in mesothelial cells of lung cancer leads to an inflammatory response that fuels cancer initiation and progression and then activates the NF-kappaB-signaling pathway in lung cancer, consequently increasing proliferation and inhibiting apoptosis.

NLRP3 inflammasomes mediate both suppressions of apoptosis and progression of the cell cycle by leptin dependent ROS production in breast cancer, which is mediated via estrogen receptor alpha (ERalpha)/reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase signaling.

proposed that significant cell death was observed only when P2X7R and NLRP3 inflammasome were both inhibited by ATP and MCC950, a specific inhibitor of NLRP3 inflammasome, and further research into safety manipulation of NLRP3 inflammasome without enhancing significant dose dependent side effects is required.

In addition, inactivation of NLRP3 inflammasome has also been found to reduce IL-1beta expression and halt development of melanoma.

Inactivation of NLRP3 inflammasome driven by miR-233-3p has been found to decrease the expression of NLRP3 inflammasome associated proteins, ASC, IL-1beta, and IL-18 in breast cancers and suppress tumor growth.

found that NLRP3 in renal tubular cells re-localizes from the cytosol to the mitochondria during hypoxia and binds to MAVS, which attenuates mtROS production and depolarization of the mitochondrial membrane potential under hypoxia.

Huang et al. reported that beta-catenin promotes NLRP3 inflammasome activation, and silencing of beta-catenin impairs NLRP3 activation.

TXNIP knockdown or targeting by miR-20b resulted in a pro tumorigenic phenotype with increased cell proliferation, inhibited cell senescence reduced cell cycle modulators (p16 and p21), and decreased NLRP3 inflammasome associated proteins (NLRP3 and cleaved caspase-1).

Increased activation of the NLRP3 inflammasome promotes migration and invasion activities in gastric cancer cells.

The role of NLRP3 in promoting invasion has been demonstrated with human endometrial cancer cell lines such as Ishikawa and HEC-1A cells, where knockdown of NLRP3 significantly reduces proliferation, clonogenicity, invasion and migration.

In contrast, overexpression of NLRP3 enhances the activities of proliferation, migration and invasion as well as increasing caspase-1 activation and IL-1beta secretion in human endometrial cancer cells.

Moreover, the silencing of NLRP3 significantly decreases the migration and invasion in OSCC cells and reduces EMT related protein expression.

The knockdown of NLRP3 significantly reduces the proliferation, clonogenicity, invasion and migration in both Ishikawa and HEC-1A cells, while in contrast, NLRP3 overexpression enhances the proliferation, migration and invasion in both Ishikawa and HEC-1A cells and furthermore, increases caspase-1 activation and the release of IL-1beta in endometrial cancer cells.

NLRP3 inflammasome inactivation, driven by miR-223-3p, increases proliferation, promotes invasion and inhibits apoptosis in breast cancer cells.

NLRP3 in the primary lesion of cancer cells drives the production of pro-IL-1beta, DC maturation, and the secretion of IL-1beta to support the evolution of tumor specific CD8 + T cells.

In the primary lesion of cancer cells, NLRP3 drives the production of pro-IL-1beta, DC maturation, and the secretion of IL-1beta to support the differentiation of tumor specific CD8 + T cells.

In contrast, overexpression of NLRP3 enhances the activities of proliferation, migration and invasion as well as increasing caspase-1 activation and IL-1beta secretion in human endometrial cancer cells.

NLRP3 enhances IL-1beta, subsequently activating NF-kappaB, and initiates JNK signaling to cause proliferation and invasion in gastric cancer.

NLRP3 agonist induces Wnt and beta-catenin activation, whereas inactivation of Wnt and beta-catenin results in the inhibition of NLRP3, IL-1beta.

NLRP3 inflammasome activation induced IL-1beta and IL-18 in lung cancer may work through mechanisms other than the caspase-1 pathway, indicating that NLRP3 inflammasome can mediate the release of IL-1beta and IL-18 through caspase-1-dependent or -independent pathways.

Epistasis analysis revealed that NLRP3 variants together with polymorphisms in inflammasome related genes modulate both the frequency of inflammasome activation and the process of IL-1beta and IL-18 maturation thatinfluence HPV infection outcome and cervical cancer progression (XREF_TABLE).

NLRP3 in the primary lesion of cancer cells drives the production of pro-IL-1beta, DC maturation, and the secretion of IL-1beta to support the evolution of tumor specific CD8 + T cells.

In the primary lesion of cancer cells, NLRP3 drives the production of pro-IL-1beta, DC maturation, and the secretion of IL-1beta to support the differentiation of tumor specific CD8 + T cells.

NLRP3 inflammasome activation induced IL-1beta and IL-18 in lung cancer may work through mechanisms other than the caspase-1 pathway, indicating that NLRP3 inflammasome can mediate the release of IL-1beta and IL-18 through caspase-1-dependent or -independent pathways.

Epistasis analysis revealed that NLRP3 variants together with polymorphisms in inflammasome related genes modulate both the frequency of inflammasome activation and the process of IL-1beta and IL-18 maturation thatinfluence HPV infection outcome and cervical cancer progression (XREF_TABLE).

In contrast, overexpression of NLRP3 enhances the activities of proliferation, migration and invasion as well as increasing caspase-1 activation and IL-1beta secretion in human endometrial cancer cells.

Consistently, knockdown of NLRP3 induces cell apoptosis in MCF-7 cells and decreases cell migration; nevertheless, in other cell-types, NLRP3 inflammasome may pharmacologically repress proliferation and metastasis of hepatic cell carcinoma (HCC) (XREF_TABLE).

The role of NLRP3 in promoting invasion has been demonstrated with human endometrial cancer cell lines such as Ishikawa and HEC-1A cells, where knockdown of NLRP3 significantly reduces proliferation, clonogenicity, invasion and migration.

In contrast, overexpression of NLRP3 enhances the activities of proliferation, migration and invasion as well as increasing caspase-1 activation and IL-1beta secretion in human endometrial cancer cells.

The knockdown of NLRP3 significantly reduces the proliferation, clonogenicity, invasion and migration in both Ishikawa and HEC-1A cells, while in contrast, NLRP3 overexpression enhances the proliferation, migration and invasion in both Ishikawa and HEC-1A cells and furthermore, increases caspase-1 activation and the release of IL-1beta in endometrial cancer cells.

NLRP3 inflammasome inactivation, driven by miR-223-3p, increases proliferation, promotes invasion and inhibits apoptosis in breast cancer cells.

Similarly, activation of NLRP3 inflammasome in mesothelial cells of lung cancer leads to an inflammatory response that fuels cancer initiation and progression and then activates the NF-kappaB-signaling pathway in lung cancer, consequently increasing proliferation and inhibiting apoptosis.

We suggest the opposite results in NLRP3 mediated cell proliferation due to different IL-1beta levels (XREF_TABLE).

Despite the major downstream event of NLRP3 inflammation formation of caspase-1 mediated pyroptosis, NLRP3 seems to mediate the dual-function of apoptosis and survival.

Inhibition of NLRP3 suppresses the proliferation, migration and invasion, and promotes apoptosis in glioma cells, while in contrast, increased expression of NLRP3 significantly enhances the proliferation, migration and invasion as well as attenuating apoptosis in glioma cells (XREF_TABLE).

found that NLRP3 overexpression inhibits cell proliferation and stimulates apoptosis in leukemic cells.

NLRP3 in the primary lesion of cancer cells drives the production of pro-IL-1beta, DC maturation, and the secretion of IL-1beta to support the evolution of tumor specific CD8 + T cells.

In the primary lesion of cancer cells, NLRP3 drives the production of pro-IL-1beta, DC maturation, and the secretion of IL-1beta to support the differentiation of tumor specific CD8 + T cells.

NLRP3 inflammasomes mediate both suppressions of apoptosis and progression of the cell cycle by leptin dependent ROS production in breast cancer, which is mediated via estrogen receptor alpha (ERalpha)/reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase signaling.

Moreover, NLRP3 downstream, IL-1beta, also stimulates the production of ROS that, in turn, induces DNA damage and cancer development in CRC (XREF_TABLE).

Although caspase-1 activation is the major downstream event of NLRP3 inflammasome assembly, recent studies have reported that NLRP3 inflammasome could also be activated by caspase-8.

ATP, one of the major cancer metabolites and constituents of the TME, serves as a key DAMP that activates NLRP3 inflammasome via the purinergic P2X7 receptors.

Among the known human chemokines, a co-regulated set of four (chemokine (C-C motif) ligand (CCL)-4, CCL-5, chemokine (C-X-C motif) ligand (CXCL)-9, CXCL-10) chemokines is upregulated in primary PDA carcinoma and PDA liver metastasis, which regulates CD8 + T cell infiltration, activates T cells, and promotes NLRP3 mediated T cell priming and enhances anti-tumor CD8 + T cell cytotoxic activity for an effective immune checkpoint therapy response.

The probability for the occurrence of sulphur plumes is enhanced in years with a lower annual mean of upwelling intensity, decreased oxygen supply associated with decreased lateral ventilation of bottom waters, more southern position of the Angola Benguela Frontal Zone, increased mass fraction of South Atlantic Central Water and stronger downwelling coastal trapped waves.

Interestingly, in addition to its role in inhibiting caspase-1, parthenolide also directly inhibits NLRP3 by inhibiting its ATPase activity, which is required for activation of caspase-1.

XREF_BIBR It was thought to be an NFkappaB inhibitor through selective inhibition of kappaB kinase beta (IKKbeta) kinase activity; however, in addition to its effects on NFkappaB activation, parthenolide has now been shown to inhibit activation of caspase-1 in response to NLRP3, NLRP1, and NLRC4 stimulation.

The effect of parthenolide on the spectrum of inflammasomes implies that it acts on a common component and, accordingly, it has been shown that parthenolide is a direct inhibitor of caspase-1, causing alkylation of caspase-1 on a number of cysteine residues.

IL-1beta secretion was not affected by treatment with the NLRP3 inhibitor glyburide XREF_BIBR or parthenolide, which has also been shown to inhibit NLRP3 XREF_BIBR.

Glyburide and parthenolide both inhibited NLRP3 activation by LPS and ATP (data not shown).

XREF_BIBR have shown that parthenolide directly inhibits caspase-1 by alkylation of certain cysteine residues.

Water fluxes through pressurized root systems treated with nitrogen and low oxygen (< 2% O (2)), elevated CO (2) (20% CO (2)), and low O (2) with elevated CO (2) concentrations were reduced to 40, 51 and 58%, respectively, of J (v) of plants aerated with ambient air.

On the contrary, when agouti activity is inhibited by beta-Defensin, or Corin, or beta-catenin in the DP, the yellow coat turns to be black XREF_BIBR - XREF_BIBR.

Conditional knockout of NFIB in HFSCs promotes McSCs proliferation and differentiation, indicating a role of NFIB as a regulator of McSC behavior 73.

Conditional knockout of NFIB in HFSCs promotes McSCs proliferation and differentiation, indicating a role of NFIB as a regulator of McSC behavior 73.

On the contrary, when agouti activity is inhibited by beta-Defensin, or Corin, or beta-catenin in the DP, the yellow coat turns to be black XREF_BIBR - XREF_BIBR.

On the contrary, when agouti activity is inhibited by beta-Defensin, or Corin, or beta-catenin in the DP, the yellow coat turns to be black XREF_BIBR - XREF_BIBR.

On the contrary, when agouti activity is inhibited by beta-Defensin, or Corin, or beta-catenin in the DP, the yellow coat turns to be black XREF_BIBR - XREF_BIBR.

Mechanistically, knockout of Kindlin-1 promotes cutaneous epithelial stem cells differentiation via inhibiting alpha (v) beta (6) integrin mediated TGF-beta1 liberation and promoting integrin independent Wnt ligand expression to activate Wnt and beta-catenin signaling 82.

Mechanistically, knockout of Kindlin-1 promotes cutaneous epithelial stem cells differentiation via inhibiting alpha (v) beta (6) integrin mediated TGF-beta1 liberation and promoting integrin independent Wnt ligand expression to activate Wnt and beta-catenin signaling 82.