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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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SOCS1 counteracts ROS-mediated survival signals and promotes apoptosis by modulating cell cycle to increase radiosensitivity of colorectal cancer cells

  • Ryu, Ji-Yoon (Laboratory of Immunology, Department of Biological Science, College of Natural Science, Sungkyunkwan University) ;
  • Oh, Jiyoung (Laboratory of Immunology, Department of Biological Science, College of Natural Science, Sungkyunkwan University) ;
  • Kim, Su-Min (Laboratory of Immunology, Department of Biological Science, College of Natural Science, Sungkyunkwan University) ;
  • Kim, Won-Gi (Laboratory of Immunology, Department of Biological Science, College of Natural Science, Sungkyunkwan University) ;
  • Jeong, Hana (Laboratory of Immunology, Department of Biological Science, College of Natural Science, Sungkyunkwan University) ;
  • Ahn, Shin-Ae (Laboratory of Immunology, Department of Biological Science, College of Natural Science, Sungkyunkwan University) ;
  • Kim, Seol-Hee (Laboratory of Immunology, Department of Biological Science, College of Natural Science, Sungkyunkwan University) ;
  • Jang, Ji-Young (Tumor Immunity Medical Research Center, Cancer Research Institute, Seoul National University College of Medicine) ;
  • Yoo, Byong Chul (Colorectal Cancer Branch, Research Center, National Cancer Institute) ;
  • Kim, Chul Woo (Tumor Immunity Medical Research Center, Cancer Research Institute, Seoul National University College of Medicine) ;
  • Lee, Choong-Eun (Laboratory of Immunology, Department of Biological Science, College of Natural Science, Sungkyunkwan University)
  • Received : 2021.12.31
  • Accepted : 2022.03.03
  • Published : 2022.04.30
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Abstract

As negative regulators of cytokine signaling pathways, suppressors of cytokine signaling (SOCS) proteins have been reported to possess both pro-tumor and anti-tumor functions. Our recent studies have demonstrated suppressive effects of SOCS1 on epithelial to mesenchymal signaling in colorectal cancer cells in response to fractionated ionizing radiation or oxidative stress. The objective of the present study was to determine the radiosensitizing action of SOCS1 as an anti-tumor mechanism in colorectal cancer cell model. In HCT116 cells exposed to ionizing radiation, SOCS1 over-expression shifted cell cycle arrest from G2/M to G1 and promoted radiation-induced apoptosis in a p53-dependent manner with down-regulation of cyclin B and up-regulation of p21. On the other hand, SOCS1 knock-down resulted in a reduced apoptosis with a decrease in G1 arrest. The regulatory action of SOCS1 on the radiation response was mediated by inhibition of radiation-induced Jak3/STAT3 and Erk activities, thereby blocking G1 to S transition. Radiation-induced early ROS signal was responsible for the activation of Jak3/Erk/STAT3 that led to cell survival response. Our data collectively indicate that SOCS1 can promote radiosensitivity of colorectal cancer cells by counteracting ROS-mediated survival signal, thereby blocking cell cycle progression from G1 to S. The resulting increase in G1 arrest with p53 activation then contributes to the promotion of apoptotic response upon radiation. Thus, induction of SOCS1 expression may increase therapeutic efficacy of radiation in tumors with low SOCS1 levels.

Keywords

Acknowledgement

This study was supported in part by NRF grants #20100018682, #2013M2B2A9A03051275, #2015003291, #2016911262, #2018R1A2B6002201, and 2022R1H1A2003471. H Jeong was also supported in part by 2017 Global Ph.D Fellowship.

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