A GRN Autocrine-Dependent FAM135B/AKT/mTOR Feedforward Loop Promotes Esophageal Squamous Cell Carcinoma Progression

Abstract Esophageal squamous cell carcinoma (ESCC) is one of the most common and deadly diseases. In our previous comprehensive genomics study, we found that family with sequence similarity 135 member B (FAM135B) was a novel cancer-related gene, yet its biological functions molecular mechanisms remain unclear. this demonstrate protein levels FAM135B are significantly higher in ESCC tissues than precancerous tissues, high expression correlates poorer clinical prognosis. Ectopic promoted proliferation vitro vivo, likely through direct interaction growth factor GRN, thus forming feedforward loop AKT/mTOR signaling. Patients overexpression both GRN had worse prognosis; multivariate Cox model analysis indicated an independent prognostic for patients ESCC. transgenic mice bore heavier tumor burden wild-type survived relatively shorter lifespan after 4-nitroquinoline 1-oxide treatment. addition, serum level mice, suggesting might provide diagnostic discrimination These findings suggest between plays critical roles regulation progression be potential therapeutic targets factors Significance: investigate promoting new biomarkers