Zhou J, Chen JR, Li JM, Han SQ, Deng XY, Li ZM, Tong W, Wang C, Bai Y, Zhang YM. IL-22/IL-22R1 pathway enhances cholangiocarcinoma progression via ERK1/2 activation. World J Gastrointest Oncol 2025; 17(3): 102083 [PMID: 40092929 DOI: 10.4251/wjgo.v17.i3.102083]
Corresponding Author of This Article
Ya-Min Zhang, Chief Physician, PhD, Department of Hepatobiliary Surgery, Tianjin First Central Hospital, No. 24 Fukang Road, Nankai District, Tianjin 300070, China. zhangyamin@nankai.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
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Zhou J, Chen JR, Li JM, Han SQ, Deng XY, Li ZM, Tong W, Wang C, Bai Y, Zhang YM. IL-22/IL-22R1 pathway enhances cholangiocarcinoma progression via ERK1/2 activation. World J Gastrointest Oncol 2025; 17(3): 102083 [PMID: 40092929 DOI: 10.4251/wjgo.v17.i3.102083]
World J Gastrointest Oncol. Mar 15, 2025; 17(3): 102083 Published online Mar 15, 2025. doi: 10.4251/wjgo.v17.i3.102083
IL-22/IL-22R1 pathway enhances cholangiocarcinoma progression via ERK1/2 activation
Jin Zhou, Jing-Rui Chen, Jin-Ming Li, Shuang-Qing Han, Xi-Yue Deng, Zhong-Min Li, Wen Tong, Chao Wang, Yi Bai, Ya-Min Zhang
Jin Zhou, Jing-Rui Chen, Jin-Ming Li, Shuang-Qing Han, Xi-Yue Deng, Wen Tong, Chao Wang, The First Central Clinical School, Tianjin Medical University, Tianjin 300192, China
Zhong-Min Li, Department of Hepatobiliary and Pancreatic Surgery, Tianjin Nankai Hospital, Tianjin 300070, China
Yi Bai, Ya-Min Zhang, Department of Hepatobiliary Surgery, Tianjin First Central Hospital, Tianjin 300070, China
Co-first authors: Jin Zhou and Jing-Rui Chen.
Co-corresponding authors: Yi Bai and Ya-Min Zhang.
Author contributions: Zhou J Chen JR made equal contributions to this research as co-firsts; Bai Y and Zhang YM contribute equally to this research as co-corresponding authors; Zhou J, Bai Y and Zhang YM were involved in designing the study; Zhou J, Chen JR, Li JM, Han SQ, Deng XY contributed to the bioinformatics analysis, experimental operation and data analysis; Li ZM, Tong W, Wang C participated in data analysis; Zhou J, Chen JR wrote the manuscript; Bai Y and Zhang YM critically revised the manuscript for important intellectual content; all authors read and approved the final version.
Supported by National Natural Science Foundation of China, No. 82372194.
Institutional review board statement: The research was sanctioned by the Ethics Committee of Tianjin First Central Hospital.
Institutional animal care and use committee statement: Animals experiments were approved by Animal Ethics Committee of Tianjin First Central Hospital.
Conflict-of-interest statement: The authors declare that they have no competing interests.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement:
The data sources are included in the Methods section of this article. Further information is available from the corresponding author.
Corresponding author: Ya-Min Zhang, Chief Physician, PhD, Department of Hepatobiliary Surgery, Tianjin First Central Hospital, No. 24 Fukang Road, Nankai District, Tianjin 300070, China. zhangyamin@nankai.edu.cn
Received: October 8, 2024 Revised: December 16, 2024 Accepted: January 8, 2025 Published online: March 15, 2025 Processing time: 129 Days and 7.5 Hours
Abstract
BACKGROUND
IL-22 plays a pivotal role in the processes of inflammation and tissue healing., but its role in cholangiocarcinoma (CCA) remains unclear. our study explored the IL-22/IL-22R1 pathway and its impact on CCA progression through the ERK1/2 signaling cascade.
AIM
To determine the mechanism of the IL-22/IL-22R1 pathway in CCA and provide new directions for its clinical treatment.
METHODS
IL-22R1 expression was assessed in human and rat CCA tissues utilizing immunohistochemical techniques, Western blot analysis, and quantitative reverse transcription PCR. The impact of IL-22 on CCA cells was assessed in vitro via tests for proliferation, migration, invasion, and apoptosis assays. The rat models of thioacetamide-induced CCA and subcutaneous xenografts in nude mice were used to assess the in vivo effects. ERK1/2 inhibitors were applied to elucidate the mechanistic role of the pathway.
RESULTS
IL-22R1 was overexpressed in CCA cell lines and tissues. IL-22 treatment increased the phosphorylation of ERK1/2, promoting tumor cell proliferation, migration, invasion, and resistance to apoptosis. ERK1/2 inhibition considerably reversed these effects both in vitro and in vivo.
CONCLUSION
The IL-22/IL-22R1 axis promotes CCA progression by activating ERK1/2 signaling. Targeting this pathway with ERK1/2 inhibitors offers potential therapeutic strategies for CCA.
Core Tip: This research results show that IL-22R1 is highly expressed in cholangiocarcinoma (CCA) cell lines and tissues. The binding of IL-22 to IL-22R1 forms the IL-22/IL-22R1 axis, which can promote the progression of CCA both in vivo and in vitro. The application of ERK1/2 inhibitors can reverse the promoting effect of IL-22 on CCA, providing potential therapeutic strategies for CCA’s clinical treatment.
