FAIM2 Promotes Non-Small Cell Lung Cancer Cell Growth and Bone Metastasis by Activating the Wnt/β-Catenin Pathway

FAIM2通过激活Wnt/β-Catenin通路促进非小细胞肺癌细胞生长和骨转移

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作者:Kelin She, Wensheng Yang, Mengna Li, Wei Xiong, Ming Zhou

Aim

Bone metastasis is the major reason for the poor prognosis and high mortality rate of non-small cell lung cancer (NSCLC) patients. This study explored the function and underlying mechanism of Fas apoptotic inhibitory molecule 2 (FAIM2) in the bone metastasis of NSCLC.

Conclusions

FAIM2 promoted NSCLC cell growth and bone metastasis by regulating the EMT process and Wnt/β-catenin signaling pathway. FAIM2 might be useful for diagnosing and treating NSCLC bone metastases.

Methods

Samples of normal lung tissue and NSCLC tissue (with or without bone metastasis) were collected and analyzed for FAIM2 expression. HARA cells with FAIM2 overexpression and HARA-B4 cells with FAIM2 knockdown were tested for proliferation, migration, invasion, anoikis, and their ability to adhere to osteoblasts. Next, whether FAIM2 facilitates bone metastasis by regulating the epithelial mesenchymal transformation (EMT) process and Wnt/β-catenin signaling pathway were investigated. Finally, an in vivo model of NSCLC bone metastasis was established and used to further examine the influence of FAIM2 on bone metastasis.

Results

FAIM2 was highly expressed in NSCLC tissues and NSCLC tissues with bone metastasis. FAIM2 expression was positively associated with the tumor stage, lymph node metastasis, bone metastasis, and poor prognosis of NSCLC. FAIM2 upregulation promoted HARA cell proliferation, migration, and invasion, but inhibited cell apoptosis. FAIM2 knockdown in HARA-B4 cells produced the opposite effects. HARA-B4 cells showed a stronger adhesive ability to osteocytes than did HARA cells. FAIM2 was found to be related to the adhesive ability of HARA and HARA-B4 cells to osteocytes. FAIM2 facilitated bone metastasis by regulating the EMT process and Wnt/β-catenin signaling pathway. Finally, FAIM2 was found to participate in regulating NSCLC bone metastasis in vivo. Conclusions: FAIM2 promoted NSCLC cell growth and bone metastasis by regulating the EMT process and Wnt/β-catenin signaling pathway. FAIM2 might be useful for diagnosing and treating NSCLC bone metastases.

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