Epithelial mesenchymal transition (EMT) has been shown to play a role in cellular differentiation during deve-lopment and tumor invasion. However, the precise molecular mechanisms of EMT are not fully elucidated. Previous studies suggested that the mechanism underlying the possible involvement of ezrin in EMT process might be different from that of moesin, another ERM protein. In our study, we examined the role of ezrin in actin filament reorganization and cell meta-stasis during TGF-β1-induced alveolar EMT. Suppressing ezrin expression limited morphological changes and actin filament remodeling, decreased cell migration and invasion during EMT. Immunofluorescence experiments indicated that EMT characteristics in lung cancer cells are associated to differential ezrin subcellular localization. We also found that podocalyxin interacted with ezrin after TGF-β1 induction. Therefore, ezrin is an important regulator of the EMT process, and its function might possibly be mediated by the ezrin-podocalyxin interaction during TGF-β1-induced alveolar EMT. Our finding provides important new insights into the mechanisms of action of the ERM proteins in the TGF-β1-induced alveolar EMT.
MicroRNAs (miRNAs) have critical roles in the progression of nasopharyngeal carcinoma (NPC), a highly invasive and metastatic cancer that is widely prevalent in Southern China. miR-491-5p has been implicated in multiple types of cancer; however, its biological role and underlying mechanism in NPC have not been fully explored. In the present study, we found that miR-491-5p was downregulated in NPC tissues and cell lines compared with the corresponding normal counterparts. Overexpression of miR-491-5p significantly inhibited cell proliferation, migration and invasion in vitro and suppressed tumor growth in vivo. Using miRNA target prediction algorithms and reporter assays, we showed that miR-491-5p suppressed Notch3 expression both at the mRNA and protein level through directly targeting the 3' untranslated region (3'-UTR) of Notch3 mRNA. Overexpression of Notch3 significantly reversed the tumor-suppressive effects of miR‑491-5p. Taken together, the present study reveals a mechanistic link between miR-491-5p and Notch3 in the pathogenesis of NPC and that miR-491-5p has potential as a therapeutic target for NPC.
Grb2-associated binder 1 (Gab1) is often aberrant in cancerous cells and tissues, whose alteration is responsible for aggressive phenotypes. In this study, we examined the Gab1 expression in human oral squamous cell carcinoma (OSCC) tissues and investigated the cellular and molecular effect of Gab1 on migration, invasion, and cell growth of the OSCC cell lines SCC15 and SCC25. We found that Gab1 was overexpressed in OSCC tissues and cells, which is related to the protein levels of various molecules associated with cellular proliferation, migration, and invasion. Functional assays identified that Gab1 overexpression promoted cell proliferation and invasion of OSCC cells and inhibited cell apoptosis in the SCC15 and SCC25 cell lines. On the other hand, Gab1 silencing affected the proliferation and invasion of OSCC cells and induced cell apoptosis. Western blot assay identified that Gab1 overexpression suppressed the expression of Cdc20 homolog 1 (Cdh1) and then promoted cell invasion in OSCC cells. Furthermore, Gab1-mediated Cdh1 downregulation was significantly reversed when the cells were subjected to an inhibitor of p-Akt. In conclusion, these results suggested that Gab1 induced malignant progression of OSCC cells probably via activation of the Akt/Cdh1 signaling pathway. Thus, Gab1 may be a potential therapeutic target in the treatment of OSCC patients.
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