Mitofusin-2 over-expresses and leads to dysregulation of cell cycle and cell invasion in lung adenocarcinoma

Abstract

Mitofusin-2 (MFN2) is a mitochondrial protein associated with mitochondrial fusion process. It was initially identified as a hyperplasia suppressor and implicated in Charcot-Marie-Tooth disease. Recent studies showed that MFN2 played important roles in the development of multiple tumors. Here we examined MFN2 expression in 30 lung adenocarcinoma samples and revealed that the expression of MFN2 was significantly higher in lung adenocarcinoma tissues as compared to adjacent normal tissues. We then investigated the impact of MFN2 knockdown on A549 human lung adenocarcinoma cells and showed that cell proliferation, cell cycle and invasion behavior were all deregulated by MFN2 knockdown. And deregulation of cell cycle pathway after MFN2 knockdown was confirmed by microarray analysis. Furthermore, microarray analysis also revealed that different oncogenes such as RAP1A, RALB and ITGA2 were oppositely regulated by MFN2, which provided molecular clues for the paradoxical functions of MFN2 in tumor development. Taken together, our study unraveled the tumor-promoting functions of MFN2 in lung adenocarcinoma and implicated that the role of MFN2 in cancer development might be more complicated than expected and should be explored in detail in the future.

The anti-tumor effects of Mfn2 in breast cancer are dependent on promoter DNA methylation, the P21Ras motif and PKA phosphorylation site

“…The results are consistent with previous studies in VSMCs (3) and in various types of cancer, including breast cancer (18,37) gastric cancer (18), urinary bladder carcinoma (38) and hepatocellular carcinoma (20,21,23) and lung adenocarcinoma (5,8,24,(38)(39)(40)(41). However, tumor-promoting functions of Mfn2 in lung adenocarcinoma have also been reported (42,43). These conflicting results may be due to differing experimental methods, but suggest that the roles of Mfn2 in different types of cancer are more complicated than expected.…”

Cryptolepine inhibits melanoma cell growth through coordinated changes in mitochondrial biogenesis, dynamics and metabolic tumor suppressor AMPKα1/2-LKB1

“…Higher expression of Mfn1 and Mfn2 has been linked with cancer cell proliferation, enhanced cell survival and invasion. Conversely, inhibition of Mfn1 and Mfn2 expression inhibits cell growth and induces apoptosis of various cancer cells 29, 30, 43, 50 . Expression of Opa1 also has been shown to enhance cancer cell proliferation and survival whereas its inhibition leads to apoptosis 51, 52 .…”

Dynamins and BAR Proteins-Safeguards against Cancer

“…54 Mfn 2 (which is also known as hyperplasia suppressor gene 2) has been shown to exert antitumor effects in a diverse set of cancer cells (lung, breast, gastric, bladder, liver). 55–59 Mfn2 overexpression in bladder carcinoma cells significantly inhibited cell proliferation by inducing apoptosis. 58 Significant downregulation of Mfn2 was also observed in liver cancer cells and overexpression of Mfn2 inhibited proliferation of these cells and induced apoptosis by increasing the level of caspase-3.…”