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- W3084072991 abstract "The dynamic interplay between cancer cells and cancer-associated fibroblasts (CAFs) is regulated by multiple signaling pathways, which can lead to cancer progression and therapy resistance. We have previously demonstrated that hMENA, a member of the actin regulatory protein of Ena/VASP family, and its tissue-specific isoforms influence a number of intracellular signaling pathways related to cancer progression. Here, we report a novel function of hMENA/hMENAΔv6 isoforms in tumor-promoting CAFs and in the modulation of pro-tumoral cancer cell/CAF crosstalk via GAS6/AXL axis regulation. LC-MS/MS proteomic analysis reveals that CAFs that overexpress hMENAΔv6 secrete the AXL ligand GAS6, favoring the invasiveness of AXL-expressing pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC) cells. Reciprocally, hMENA/hMENAΔv6 regulates AXL expression in tumor cells, thus sustaining GAS6-AXL axis, reported as crucial in EMT, immune evasion, and drug resistance. Clinically, we found that a high hMENA/GAS6/AXL gene expression signature is associated with a poor prognosis in PDAC and NSCLC. We propose that hMENA contributes to cancer progression through paracrine tumor-stroma crosstalk, with far-reaching prognostic and therapeutic implications for NSCLC and PDAC." @default.
- W3084072991 created "2020-09-14" @default.
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- W3084072991 date "2020-09-10" @default.
- W3084072991 modified "2023-10-18" @default.
- W3084072991 title "The actin modulator <scp>hMENA</scp> regulates <scp>GAS</scp> 6‐ <scp>AXL</scp> axis and pro‐tumor cancer/stromal cell cooperation" @default.
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- W3084072991 doi "https://doi.org/10.15252/embr.202050078" @default.
- W3084072991 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7645265" @default.
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- W3084072991 hasPublicationYear "2020" @default.
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