Open Access

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

  • Authors:
    • Yan Sun
    • Man Luo
    • Guilin Chang
    • Weiying Ren
    • Kefen Wu
    • Xi Li
    • Jiping Shen
    • Xiaoping Zhao
    • Yu Hu
  • View Affiliations

  • Published online on: September 27, 2017     https://doi.org/10.3892/ol.2017.7085
  • Pages:7323-7331
  • Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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 Ser6 of hnRNPA1 facilitated hnRNPA1 binding to the splicing site of the PKM gene. As a result, cancer cells preferentially expressed the PKM2 isoform, instead of the PKM1 isoform. Furthermore, Cox regression analysis demonstrated that the phosphorylation of Ser6 of hnRNPA1 was a predictor of poor prognosis for patients with CRC. Therefore, the results of the present study revealed that the phosphorylation of Ser6 in hnRNPA1 by S6K2 was a novel mechanism underlying glucose metabolic reprogramming, and suggested that S6K2 is a potential therapeutic target for CRC treatment.

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December 2017
Volume 14 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

2016 Impact Factor: 1.39
Ranked #68/217 Oncology
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APA
Sun, Y., Luo, M., Chang, G., Ren, W., Wu, K., Li, X. ... Hu, Y. (2017). Phosphorylation of Ser6 in hnRNPA1 by S6K2 regulates glucose metabolism and cell growth in colorectal cancer. Oncology Letters, 14, 7323-7331. https://doi.org/10.3892/ol.2017.7085
MLA
Sun, Y., Luo, M., Chang, G., Ren, W., Wu, K., Li, X., Shen, J., Zhao, X., Hu, Y."Phosphorylation of Ser6 in hnRNPA1 by S6K2 regulates glucose metabolism and cell growth in colorectal cancer". Oncology Letters 14.6 (2017): 7323-7331.
Chicago
Sun, Y., Luo, M., Chang, G., Ren, W., Wu, K., Li, X., Shen, J., Zhao, X., Hu, Y."Phosphorylation of Ser6 in hnRNPA1 by S6K2 regulates glucose metabolism and cell growth in colorectal cancer". Oncology Letters 14, no. 6 (2017): 7323-7331. https://doi.org/10.3892/ol.2017.7085