FAM3B promotes progression of oesophageal carcinoma via regulating the AKT–MDM2–p53 signalling axis and the epithelial‐mesenchymal transition

Song‐Lin He,Long‐Qi Chen,Wen‐Ping Wang,Li‐Yan Xu,En‐Min Li,Yu‐Sang Yang

doi:10.1111/jcmm.14040

Abstract

FAM3B has been suggested to play important roles in the progression of many cancers, such as gastric, oral, colon and prostate cancer. However, little is known about the role of FAM3B in human esophageal squamous cell carcinoma (ESCC). In the present study, we found that FAM3B expression was higher in ESCC tissues than in adjacent normal tissues. Using quantitative real‐time polymerase chain reaction, we found similar results in cell lines. FAM3B expression was significantly related to T/TNM stage. Importantly, Kaplan–Meier analysis revealed that a high expression level of FAM3B predicted a poor outcome for ESCC patients. Overexpression of FAM3B inhibits ESCC cell death, increases oesophageal tumour growth in xenografted nude mice, and promotes ESCC cell migration and invasion. Further studies confirmed that FAM3B regulates the AKT–MDM2–p53 pathway and two core epithelial‐to‐mesenchymal transition process markers, Snail and E‐cadherin. Our results provide new insights into the role of FAM3B in the progression of ESCC and suggest that FAM3B may be a promising molecular target and diagnostic marker for ESCC.

Highlights

Esophageal squamous cell carcinoma (ESCC) is the leading cause of cancer death in China.[1–3] According to the 2015 Chinese Cancer Statistics, the morbidity of oesophageal cancer ranked 5th and its mortality ranked 4th among all kinds of malignant tumours.[4]
Several molecular markers closely associated with tumour progression have been recognized, more sensitive markers are needed because of the poor prognosis of ESCC patients
A few studies have provided evidence that FAM3B is associated with tumour progression

Summary

| INTRODUCTION

Esophageal squamous cell carcinoma (ESCC) is the leading cause of cancer death in China.[1–3] According to the 2015 Chinese Cancer Statistics, the morbidity of oesophageal cancer ranked 5th and its mortality ranked 4th among all kinds of malignant tumours.[4]. Intensive studies have suggested that members of the FAM3 gene family may play an important role in the development of a variety of major diseases, including diabetes and cancer.[12–15]. The regulatory role of FAM3B in the progression of other tumours, including oral squamous cell carcinoma and colon and prostate cancer, have been reported.[18–20]. Another FAM3 family member, FAM3C, was reported to be closely involved in the development of oesophageal cancer.[21]. These studies have increased interest in exploring whether FAM3B plays an important role in the progression of oesophageal cancer. Our results suggest that FAM3B may be a new therapeutic target and diagnostic marker for ESCC

| MATERIALS AND METHODS

| RESULTS

Findings

| DISCUSSION