TMEM107 inhibits EMT and invasion of NSCLC through regulating the Hedgehog pathway

Transmembrane protein 107 (TMEM107) is a key regulator of the cilium composition and Hedgehog signaling. Lower TMEM107 gene copies are correlated with poor prognosis in non-small cell lung carcinoma (NSCLC). However, TMEM107 protein expression, localization, and function in NSCLC remain unclear.

These results indicate that TMEM107 inhibits EMT and invasion by negatively regulating Hedgehog signaling and that it is downregulated in NSCLC. Key points: TMEM107 expression is lower in NSCLC tissues and correlates with poor prognosis TMEM107 inhibits invasion of NSCLC cells TMEM107 inhibits EMT of NSCLC cells Downregulation of TMEM107 activates the Hedgehog signaling pathway Downregulation of TMEM107 promotes EMT and migration in NSCLC by activating the Hedgehog signaling pathway.

We first evaluated TMEM107 expression in 12 newly diagnosed cases of NSCLC and paired adjacent healthy tissues by western blotting. We then used an immunohistochemical method to detect TMEM107 expression in 106 paraffin-embedded NSCLC and corresponding normal samples and analyzed its relationship with clinicopathological parameters. Moreover, we determined the impact of TMEM107 upregulation and downregulation on invasion, EMT and Hedgehog pathway in NSCLC cells.

Our results showed that TMEM107 is localized in the cytoplasm and that its expression was lower in NSCLC. TMEM107 expression was positively correlated with cell differentiation and negatively correlated with lymph node metastasis. In A549 and HCC460 cells, downregulation of TMEM107 facilitated cell invasion and upregulated the expression of the Hedgehog pathway target protein Gli1, invasion-associated proteins N-cadherin, vimentin, MMP2, and MMP9, and epithelial-mesenchymal transition (EMT), and inhibited the expression of E-cadherin. Treatment with the Hedgehog pathway inhibitor GANT61 attenuated TMEM107-knockdown-induced EMT and invasiveness. Conclusions: These results indicate that TMEM107 inhibits EMT and invasion by negatively regulating Hedgehog signaling and that it is downregulated in NSCLC. Key points: TMEM107 expression is lower in NSCLC tissues and correlates with poor prognosis TMEM107 inhibits invasion of NSCLC cells TMEM107 inhibits EMT of NSCLC cells Downregulation of TMEM107 activates the Hedgehog signaling pathway Downregulation of TMEM107 promotes EMT and migration in NSCLC by activating the Hedgehog signaling pathway.