FAM83G promotes proliferation, invasion, and metastasis by regulating PI3K/AKT signaling in hepatocellular carcinoma cells

Abstract

Hepatocellular carcinoma (HCC) has received extensive attention from clinical and scientific researchers due to its high incidence and refractory nature. Searching for HCC prognostic markers and gene therapy targets are key research efforts. The FAM83 protein family has been reported to promote tumor growth and metastasis in a variety of tumors, and many of its members are closely related to HCC. Multiple public databases showed that FAM83G is highly expressed in HCC patients and is associated with poor prognosis, but there is currently no relevant research evidence to verify its exact role in HCC. Through clinical data analysis, we found that increased expression of FAM83G is associated with early HCC metastasis and a high recurrence rate and indicates a poor survival rate. Both in vivo and in vitro experiments confirmed that FAM83G overexpression significantly promoted the proliferation, migration, and invasion of HCC cells, while inhibiting its expression reversed the above results. Mechanistic analysis indicated that FAM83G overexpression was accompanied by over-activation of PI3K/AKT pathway signaling, a combined increase of Cyclin D1 protein and decrease of p21 protein, and increased expression of EMT-related signal, which was manifested in the decrease of E-cadherin and the increase of N-cadherin and snail. Finally, we found that FAM83G activated PI3K/AKT signaling by directly binding with the PI3K-p85 subunit to promote its phosphorylation. In conclusion, FAM83G, as a tumor-promoting factor, can predict the poor prognosis of HCC patients and can significantly promote the proliferation, invasion, and migration of HCC cells by stimulating the PI3K/AKT signaling pathway and related downstream signals.