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Akt regulates RSK2 to alter phosphorylation level of H2A.X in breast cancer

Zhi-Feng Guo1, Fan-Long Kong1

  • 1Department of Oncology, Section II, Chifeng Municipal Hospital, Chifeng, Inner Mongolia Autonomous Region 024000, P.R. China.

Oncology Letters
|February 12, 2021
PubMed

Insights

Akt phosphorylates RSK2, inhibiting H2A.X phosphorylation. This mechanism promotes breast cancer cell survival and migration, offering new therapeutic targets for cancer treatment.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Biochemistry

Background:

  • Histone H2AX (H2A.X) phosphorylation signifies DNA damage and influences tumor progression.
  • Akt activity is inversely correlated with H2A.X phosphorylation at Ser16 (H2A.X S16ph), but the underlying mechanism is unclear.

Purpose of the Study:

  • To elucidate the mechanism connecting Akt and H2A.X S16ph.
  • To investigate the role of this interaction in breast cancer pathogenesis and oncogenic activity.

Main Methods:

  • Western blot analysis to assess protein interactions (p-Akt, H2A.X S16ph, p-RSK2).
  • Immunoprecipitation and chromatin immunoprecipitation to confirm Akt, RSK2, and H2A.X interactions in breast cancer cells.
  • MTT assays, soft agar colony formation, and cell migration experiments to evaluate cellular proliferation and migration. RT-qPCR to analyze cancer-promoting genes like PSAT-1.

Main Results:

  • Akt phosphorylates ribosomal S6 kinase 2 (RSK2) at Ser19.
  • Akt-mediated RSK2 phosphorylation inhibits H2A.X phosphorylation.
  • This pathway promotes breast cancer cell survival and migration by altering RSK2-histone binding.

Conclusions:

  • Akt-RSK2 signaling pathway regulates H2A.X phosphorylation.
  • This regulation promotes oncogenic activity in breast cancer.
  • Findings offer novel insights into breast cancer pathogenesis and potential therapeutic strategies.
Keywords:
Aktbreast cancerhistone H2AXphosphorylationserine/threonine kinase ribosomal S6 kinase 2

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