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

Guo,Zhi-Feng; Kong,Fan-Long

doi:10.3892/ol.2021.12448

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

Authors:
- Zhi-Feng Guo
- Fan-Long Kong
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Affiliations: Department of Oncology, Section II, Chifeng Municipal Hospital, Chifeng, Inner Mongolia Autonomous Region 024000, P.R. China
Published online on: January 6, 2021 https://doi.org/10.3892/ol.2021.12448
Article Number: 187
Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Histone H2AX (H2A.X) is a variant of the histone H2A family. Phosphorylation of H2A.X is a marker of DNA strand breaks and the presence or absence of H2A.X is closely related to tumor susceptibility and drug resistance. The present study found that the activity of the serine/threonine kinase Akt was negatively associated with H2A.X phosphorylated at the Ser16 site (H2A.X S16ph), but the mechanism of the inverse relationship remains elusive. The aim of the present study was to elucidate the mechanism of action between Akt and H2A.X S16ph and the exact role of this mechanism. Western blot analysis was performed to detect the regulatory association between p‑Akt and H2A.X S16ph/p‑RSK2, and immunoprecipitation and chromatin immunoprecipitation were performed to prove that Akt, RSK2 and H2A.X combine and interact in human breast cancer cells. The changes of cellular proliferation and migration induced by the interaction of Akt, RSK2 and H2A.X was determined by MTT, soft agar colony formation and cell migration experiments. The effect of interaction of Akt, RSK2 and H2A.X on cancer‑promoting genes, such as PSAT‑1 was determined via reverse transcription‑quantitative PCR analysis. The current study indicated that the serine/threonine kinase ribosomal S6 kinase 2 (RSK2) as a kinase of H2A.X could be phosphorylated by Akt at Ser19 site. Moreover, Akt positively regulated the phosphorylation of RSK2 to inhibit phosphorylation of H2A.X, thereby affecting the affinity between RSK2 and substrate histone, promoting the survival and migration of breast cancer cells. In conclusion, Akt‑mediated phosphorylation of RSK2 regulated the phosphorylation of H2A.X, thereby promoting oncogenic activity. This finding provides new insights to understand the pathogenesis and treatment mechanisms of breast cancer.

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