Functional loss of TAGLN inhibits tumor growth and increases chemosensitivity of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the leading cause of tumor mortality worldwide. However, the mechanisms underlying NSCLC tumorigenesis are incompletely understood. TAGLN, also named SM22, as a member of the calponin family, is highly expressed in many types of tumors. Nevertheless, its effects on NSCLC progression remain unclear. In this study, we found that TAGLN was over-expressed in tumor tissues of NSCLC patients and cell lines. Additionally, NSCLC patients with high expression showed worse overall survival rate. Then, gene silencing results indicated that TAGLN knockdown markedly inhibited proliferation and induced apoptosis in NSCLC cells, while rescue study exhibited opposite results. Moreover, suppressing TAGLN significantly reduced migration and invasion of NSCLC cells, and its over-expression promoted the migratory and invasive activities of NSCLC cells. The in vivo studies confirmed the oncogenic roles of TAGLN in NSCLC, along with clearly elevated metastasis. Notably, these effects were abrogated in mice with TAGLN deletion. Finally, we found that TAGLN knockdown could improve the sensitivity of NSCLC cells to sorafenib (SFB) and 5-FU treatment, further suppressing the proliferation, migration and invasion of NSCLC cells. Consistently, TAGLN deletion attenuated tumor xenografts growth and metastasis of NSCLC in mouse models by enhancing the anti-cancer effects of SFB and 5-FU. Altogether, these findings demonstrated that TAGLN functioned as an oncogene as well as a chemotherapeutic regulator during NSCLC development, which suggested a potential therapeutic strategy for NSCLC treatment mainly through repressing TAGLN expression.

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