FAM172A controls endoplasmic reticulum (ER) stress related to NF-κB signaling pathway in hepatocellular carcinoma

Abstract

Our previous investigation suggested that FAM172A shows significantly low expression in hepatocellular carcinoma. However, its mechanism is not very clear. This study showed that the FAM172A proteins are related to ER stress. FAM172A promoted the expression of NF-κB in liver cancer cells and induced ER stress through the PERK–eIF2α pathway in liver cancer cells. FAM172A could be a secreted protein and could restrain the proliferation of hepatoma cells through suppressing the cell cycle. In addition, FAM172A could also promote apoptosis or differentiation of hepatoma cells. FAM172A protein interacted with Notch 1–4 and NF-κB. The FAM172A recombinant proteins suppressed tumor formation in a mouse xenograft model. These results indicated that FAM172A could be an anti-oncogene and plays a vital role in controlling cell proliferation and the cell cycle by inducing the arrest of the G1/S phase through PERK/eIF2α via an ER stress-independent pathway and correlates with NF-κB. FAM172A, which could act as a novel treatment target of HCC.