FAM83A signaling induces epithelial-mesenchymal transition by the PI3K/AKT/Snail pathway in NSCLC.

Fengrui Zhou,Fang Yang,Shanqi Xu,Fang Liu,Bo Pan,Jianxiong Geng,Kexin Chen,Yan Yu,Qingwei Meng

doi:10.18632/aging.102163

Abstract

Family with sequence similarity 83, member A (FAM83A), as a potential tumor promoter, was reported to contribute to the progression of several malignant tumors. However, the significance of FAM83A in invasion and metastasis of non-small cell lung cancer (NSCLC) remains largely unknown. In this study, we found that FAM83A expression was significantly increased in NSCLC tissues. High expression of FAM83A was positively associated with tumor metastasis and poor survival of NSCLC patients. Functional experiments revealed that FAM83A knockdown could suppress NSCLC cell migration and invasion both in vivo and in vitro. While opposite results were observed in FAM83A-transfected cells. Mechanically, we found that FAM83A promoted NSCLC cell migration and invasion by inducing epithelial-mesenchymal transition (EMT) via PI3K/ATK/Snail signaling. Rescue experiment demonstrated that inhibition of either AKT or Snail could partially counteract the promoting effect of FAM83A overexpression in NSCLC metastasis. Taken together, our findings are the first time to demonstrate that increased expression of FAM83A in NSCLC was correlated with EMT and tumor metastasis, which may provide a novel therapeutic target in NSCLC treatment.

Highlights

Lung cancer remains the most prevalent cause of global cancer-related mortality, leading to over a million deaths each year [1]
Immunohistochemical staining confirmed that high expression of FAM83A in non-small cell lung cancer (NSCLC) was associated with metastatic clinicopathologic features and a poor prognosis
Recent discoveries have revealed that the elevated expression of FAM83A occurs in a substantial fraction of cancers [23,24,25,26,27,28]

Summary

Introduction

Lung cancer remains the most prevalent cause of global cancer-related mortality, leading to over a million deaths each year [1]. More than 79% of lung cancer patients develop metastasis, and the 5-year survival rate of these patients is less than 5% [4]. Metastasis accounts for poor prognosis and high mortality rates in non-small lung cancer (NSCLC) [5]. A hallmark of EMT is the functional loss of E-cadherin and store of Vimentin and N-cadherin (mesenchymal markers) [10,11,12]. It is often regulated by several signal pathways and transcription factors such as Snail and Twist [13,14,15,16]. Numerous studies have focused on complex regulatory networks that modulate EMT to explain and discover new mechanisms involved in cancer progression and metastasis

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Conclusion