FAM129A promotes invasion and proliferation by activating FAK signaling pathway in non-small cell lung cancer.

Abstract

Family with sequence similarity 129, member A (FAM129A), also called Niban or C1orf24, was initially identified from a rat model of hereditary renal carcinoma. FAM129A inhibited apoptosis and promoted migration and proliferation in human cancers. However, little is known about the downstream signaling during tumor progression. Our data showed that FAM129A played an oncogenic role in non-small cell lung carcinoma (NSCLC), which upregulated the protein levels of MMP2 and Cyclin D1 through activating the FAK signaling pathway. Treatment by FAK inhibitor counteracted the increase of MMP2 and Cyclin D1 expression following by FAM129A transfection through attenuating the phosphorylation of FAK. Results of immunohistochemistry revealed that the expression of FAM129A was significantly associated with larger tumor size (P=0.036), advanced TNM stage (P<0.001), and lymph node metastasis (P=0.001). Subsequent Kaplan-Meier analysis indicated that patients with FAM129A expression presented with poorer clinical outcome (P=0.001). Taken together, our results suggested that FAM129A may promote tumor proliferation and invasion of NSCLC through facilitating the phosphorylation of FAK and upregulated MMP2 and Cyclin D1. Overexpression of FAM129A may be a prognostic predictor in NSCLC patients.