Phosphorylation of Ser6 in hnRNPA1 by S6K2 regulates glucose metabolism and cell growth in colorectal cancer.

Abnormal glucose metabolism is critical in colorectal cancer (CRC) development. Expression of the pyruvate kinase (PK) M2 isoform, rather than the PKM1 isoform, serves important functions in reprogramming the glucose metabolism of cancer cells. Preferential expression of PKM2 is primarily driven by alternative splicing, which is coordinated by a group of splicing factors including heterogeneous nuclear ribonucleoprotein (hnRNP)A1, hnRNPA2 and RNA binding motif containing. However, the underlying molecular mechanisms associated with cancer cell expression of PKM2, instead of PKM1, remain unknown. The mRNA levels of PKM isoform and glucose metabolism were analyzed in CRC cells. The results of the present study indicated that S6 kinase 2 (S6K2) promotes glycolysis and growth of CRC cells by regulating alternative splicing of the PKM gene. In addition, chromatin immunoprecipitation assay indicated that S6K2 phosphorylation of Ser