FAM163A, a positive regulator of ERK signaling pathway, interacts with 14-3-3β and promotes cell proliferation in squamous cell lung carcinoma.

Abstract

PurposeFAM163A, also called neuroblastoma-derived secretory protein (NDSP) or C1ORF76, was newly found on chromosome 1q25.2. Previous studies of FAM163A focused on its expression and function in neuroblastoma. However, using an online database, we found that FAM163A may predict poor prognosis in lung squamous cell carcinomas (LUSC). Therefore, the role of FAM163A plays in LUSC needs to be further clarified.Patients and methodsWestern blots, immunofluorescence and immunohistochemistry were used to detect the effect of FAM163A on mediating cell proliferation in vitro and in vivo. Co-immunoprecipitation and immunofluorescence were utilized to evaluate the interaction and co-localization of FAM163A with 14-3-3β and ERK.ResultsIn this study, our data revealed that FAM163A overexpression increased the levels of ERK and p90RSK phosphorylation and promoted the expression of cyclin D1. Incorporation with U0126 reversed the effects of FAM163A overexpression. FAM163A directly interacted with both 14-3-3β and ERK and regulated the phosphorylation of ERK by upregulating the protein level of 14-3-3β. Immunohistochemistry results also showed that FAM163A expression significantly correlated with larger tumor size (P=0.023), TNM staging (P=0.015) and regional lymph node metastasis (P=0.016). Kaplan-Meier survival analysis implied the mean survival time of patients with positive FAM163A expression (49.72±3.97 months) was much shorter than the patients with negative FAM163A expression (63.36±3.14 months, P=0.011).ConclusionIn summary, the present study identified a novel mechanism that FAM163A, through binding and upregulating 14-3-3β, facilitated ERK phosphorylation that led to an increase of cellular proliferation of LUSC cells. FAM163A may be a useful marker to predict poor prognosis of patients with LUSC.