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    1. SLC6A14, a Na+/Cl−-coupled amino acid transporter, functions as a tumor promoter in colon and is a target for Wnt signaling

      [Paper-level Aggregated] PMCID: PMC7182441

      Evidence Type(s): Functional, Oncogenic

      Justification: Functional: The text describes the use of alpha-MT to block SLC6A14 function in colon cancer cells, demonstrating that this blockade leads to amino acid starvation and subsequent changes in marker expression, indicating a functional role of SLC6A14 in amino acid nutrition. Oncogenic: The study evaluates the effects of SLC6A14 blockade in a colon cancer cell line (LS174T), suggesting that SLC6A14 may play a role in the oncogenic process by influencing amino acid availability and mTOR signaling in cancer cells.

      Gene→Variant (gene-first): RPS6KB1(6198):S6

      Genes: RPS6KB1(6198)

      Variants: S6

    2. alpha-MT is a non-transportable blocker of SLC6A14 and thus can be used to achieve pharmacologic blockade of the transporter function. We have used this strategy successfully in two other SLC6A14-positive cancers, namely

      [Paragraph-level] PMCID: PMC7182441 Section: RESULTS PassageIndex: 5

      Evidence Type(s): Functional, Oncogenic

      Justification: Functional: The passage discusses how the variant SLC6A14 affects amino acid transport and starvation, indicating that the blockade of its function alters molecular processes such as the expression of specific markers and the phosphorylation status of mTOR and S6 kinase. Oncogenic: The variant SLC6A14 is implicated in tumor behavior, as the study evaluates its role in colon cancer cell lines, suggesting that it contributes to tumor development or progression through its function in amino acid transport and mTOR signaling.

      Gene→Variant (gene-first): 6198:S6

      Genes: 6198

      Variants: S6