CAF-secreted CXCL1 conferred radioresistance by regulating DNA damage response in a ROS-dependent manner in esophageal squamous cell carcinoma

Cell Death & Disease
Hongfang ZhangShixiu Wu

Abstract

Five-year survival rate of esophageal squamous cell carcinoma (ESCC) patients treated with radiotherapy is <20%. Our study aimed to investigate whether cancer-associated fibroblasts (CAFs), one major component of tumor microenvironment, were involved in tumor radioresistance in ESCC. By use of human chemokine/cytokine array, human chemokine CXCL1 was found to be highly expressed in CAFs compared with that in matched normal fibroblasts. Inhibition of CXCL1 expression in CAFs significantly reversed CAF-conferred radioresistance in vitro and in vivo. CAF-secreted CXCL1 inhibited the expression of reactive oxygen species (ROS)-scavenging enzyme superoxide dismutase 1, leading to increased ROS accumulation following radiation, by which DNA damage repair was enhanced and the radioresistance was mediated. CAF-secreted CXCL1 mediated the radioresistance also by activation of Mek/Erk pathway. The cross talk of CAFs and ESCC cells induced CXCL1 expression in an autocrine/paracrine signaling loop, which further enhanced tumor radioresistance. Together, our study highlighted CAF-secreted CXCL1 as an attractive target to reverse tumor radioresistance and can be used as an independent prognostic factor of ESCC patients treated with chemoradi...Continue Reading

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Citations

May 19, 2019·Cell Communication and Signaling : CCS·Zhanhuai WangWei Yu
May 16, 2020·Oxidative Medicine and Cellular Longevity·Can LuChen Chen
Nov 6, 2018·International Journal of Oncology·Shuang WangQiang Liu
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Aug 11, 2020·Oxidative Medicine and Cellular Longevity·Gan Huang, Shu-Ting Pan
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Mar 10, 2021·Journal of Cancer Research and Clinical Oncology·Hongfang ZhangShenglin Ma
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Jun 23, 2021·Journal of Experimental & Clinical Cancer Research : CR·Irma TelarovicMartin Pruschy
Aug 21, 2021·Frontiers in Cell and Developmental Biology·Yue FengYunyan Zhang

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
xenograft
transfection
biopsy
PCR
ELISA
antibody array

Software Mentioned

SPSS

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