Abstract
AimBone 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.MethodsSamples 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.ResultsFAIM2 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.ConclusionsFAIM2 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.
Highlights
Lung cancer is one of the most malignant cancers and accounts for nearly 12% of all human cancers worldwide, making it the leading cause of cancer-related death in both men and women [1]
Those results showed that when compared to normal lung tissues, Fas apoptotic inhibitory molecule 2 (FAIM2) was more highly expressed in nonsmall cell lung cancer (NSCLC) tissues (P < 0.05 or P < 0.01, Figure 1A)
Our results indicated that a high level of FAIM2 predicted a poor prognosis for NSCLC patients, including shorter disease-free survival (DFS) and overall survival (OS) times (Figure 1E)
Summary
Lung cancer is one of the most malignant cancers and accounts for nearly 12% of all human cancers worldwide, making it the leading cause of cancer-related death in both men and women [1]. In NSCLC patients, bone tissue is a frequent site of metastasis and accounts for 13.2% of all metastasis sites [5]. Bone metastasis is a negative prognostic factor for NSCLC, the molecular mechanism of bone metastasis remains largely unknown [6, 7]. An upregulation of LIGHT/tumor necrosis factor superfamily member 14 (TNFSF14) signaling was found to result in the destruction of bone homeostasis in NSCLC patients and subsequent bone metastasis [8]. Wu et al [9] reported that an ERBB2 mutation existed in 2% of NSCLC patients, and was responsible for bone metastasis. More investigations are needed to further explore the molecular mechanism of bone metastasis in NSCLC patients
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