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

BACKGROUND: 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. METHODS: 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. RESULTS: 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.

[BMP7 signaling via BMPR1A, BMPR1B inhibits the proliferation of lung large carcinoma NCI-H460 cell].

BACKGROUND AND OBJECTIVE: It has been demonstrated that bone morphogenetic protein 7 (BMP7) may both inhibit and enhance cell proliferation of many kinds of cancers, but the impact of BMP7 on lung cancer cells and the exact mechanisms are not clear. The aim of this study is to investigate the effect of BMP7 on proliferation of lung carcinoma cells and explore the roles of different types of I receptors in BMP7 signal transmission by blocking endogenous BMPRIs. METHODS: The levels of expression of BMPIRs (BMP7 type I receptors) mRNA in four different NSCLC (human non-small cell lung tumor) cell lines and HBE (normal human bronchial epithelial) cell were detected by RT-PCR. The responsiveness of pulmonary large carcinoma NCI-H460 cell to BMP7 treatment as well as to a combination of BMP7 and anti-BMPIRs treatment in proliferation were detected by MTT. RESULTS: RT-PCR showed that NCI-H460 cells expressed all three types of BMPIRs; MTT showed that BMP7 inhibit the proliferation of NCI-H460 cell line. Blocking endogenous BMPR1A, BMPR1B obviously reversed the inhibition of BMP7 on the proliferation of NCI-H460 cell respectively (P = 0.003, P = 0.014). Moreover, blocking both endogenous BMPR1A and BMPR1B almost offset the effect of BMP7 on the proliferation of NCI-H460 cell completely (P < 0.001). But ACVR1A blocking did not affect the proliferation of NCI-H460 cell et al (P = 0.074). CONCLUSIONS: BMP7 signaling via BMPR1A and BMPR1B inhibits the proliferation of pulmonary large carcinoma cell NCI-H460.