PSAT1 regulates cyclin D1 degradation and sustains proliferation of non-small cell lung cancer cells.

摘要: Multiple nodes in the one-carbon metabolism pathway play important regulatory roles cancer cell growth and tumorigenesis. The specific biological functions of metabolic enzymes regulating signaling pathways that are associated with tumor survival, however, remain unclear. Our current study found phosphoserine aminotransferase 1 (PSAT1), an enzyme catalyzing serine biosynthesis, was significantly up-regulated non-small lung (NSCLC) involved regulation E2F activity. Loss- gain-of-function experiments demonstrated PSAT1 promoted cycle progression, proliferation Mechanistic suggested elevated led to inhibition cyclin D1 degradation subsequently alteration Rb-E2F activity, which turn enhanced G1 progression NSCLC cells. Moreover, phosphorylation at threonine 286 by GSK-3β required for PSAT1-induced blockage degradation. We also activity p70S6K mediated effects on further identified over-expressed predicted poor clinical outcome patients disease. Correlation analysis showed expression positively correlated levels phosphorylated GSK-3β, Rb primary tumors. These findings uncover a mechanism constitutive activation via unrestrained occurs may represent prognostic biomarker therapeutic target.