Research Paper Volume 11, Issue 16 pp 6069—6088
FAM83A signaling induces epithelial-mesenchymal transition by the PI3K/AKT/Snail pathway in NSCLC
- 1 Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, China
- 2 Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, China
received: April 2, 2019 ; accepted: August 5, 2019 ; published: August 24, 2019 ;https://doi.org/10.18632/aging.102163
How to Cite
Copyright © 2019 Zhou et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY 3.0) License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
NSCLC: non-small cell lung cancer; OS: overall survival; PFS: progression-free survival; EMT: epithelial to mesenchymal transition; p-AKT: phosphorylation of AKT; p-PI3K: phosphorylation of PI3K.