Ribosomal Protein S6: A Potential Therapeutic Target against Cancer?

Int J Mol Sci. 2021 Dec 21;23(1):48. doi: 10.3390/ijms23010048.


Ribosomal protein S6 (RPS6) is a component of the 40S small ribosomal subunit and participates in the control of mRNA translation. Additionally, phospho (p)-RPS6 has been recognized as a surrogate marker for the activated PI3K/AKT/mTORC1 pathway, which occurs in many cancer types. However, downstream mechanisms regulated by RPS6 or p-RPS remains elusive, and the therapeutic implication of RPS6 is underappreciated despite an approximately half a century history of research on this protein. In addition, substantial evidence from RPS6 knockdown experiments suggests the potential role of RPS6 in maintaining cancer cell proliferation. This motivates us to investigate the current knowledge of RPS6 functions in cancer. In this review article, we reviewed the current information about the transcriptional regulation, upstream regulators, and extra-ribosomal roles of RPS6, with a focus on its involvement in cancer. We also discussed the therapeutic potential of RPS6 in cancer.

Keywords: anticancer; biomarker; cancer therapeutics; drug resistance; ribosomal protein S6; therapeutic target.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Proliferation / physiology
  • Humans
  • Mechanistic Target of Rapamycin Complex 1 / metabolism
  • Neoplasms / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Ribosomal Protein S6 / metabolism*
  • Signal Transduction / physiology


  • Ribosomal Protein S6
  • Mechanistic Target of Rapamycin Complex 1
  • Proto-Oncogene Proteins c-akt