title: Interleukin 22 protects colorectal cancer cells from chemotherapy by activating the STAT3 pathway and inducing autocrine expression of interleukin 8.
abstract: Resistance to chemotherapy is the major cause of colorectal cancer (CRC) treatment failure. The cytokine IL-22, which is produced by T cells and NK cells, is associated with tumorigenesis and tumor progression in cancers. However, the role of IL-22 in chemoresistance has not been investigated. We found that IL-22 levels in tumor tissues and peripheral blood were associated with chemoresistance and indicate poor prognosis for patients who received FOLFOX chemotherapy. In CRC cells, IL-22 was able to attenuate the cytotoxic and apoptosis-inducing effects of 5-FU and OXA by activating the STAT3 pathway and subsequently increasing the expression of anti-apoptotic genes. In addition, IL-22 conferred resistance to 5-FU and OXA by inducing IL-8 autocrine expression through STAT3 activation. Our findings identify IL-22 as a novel chemoresistance cytokine and may be a useful prognostic biomarker for CRC patients receiving FOLFOX chemotherapy.
authors: Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Kongjiang Road 1665, Shanghai, 200092, China. Electronic address: wtyscu@163.com.
authors: Tingyu
authors: T
authors: Wu
authors: Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Kongjiang Road 1665, Shanghai, 200092, China. Electronic address: zhongchuanwang@aliyun.com.
authors: Zhongchuan
authors: Z
authors: Wang
authors: Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Kongjiang Road 1665, Shanghai, 200092, China. Electronic address: aeolus304@sina.com.
authors: Yun
authors: Y
authors: Liu
authors: Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Kongjiang Road 1665, Shanghai, 200092, China. Electronic address: herrmayor@126.com.
authors: Zubing
authors: Z
authors: Mei
authors: Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Kongjiang Road 1665, Shanghai, 200092, China. Electronic address: wgh_0625@163.com.
authors: Guanghui
authors: G
authors: Wang
authors: Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Kongjiang Road 1665, Shanghai, 200092, China. Electronic address: xhgclzl@126.com.
authors: Zhonglin
authors: Z
authors: Liang
authors: Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Kongjiang Road 1665, Shanghai, 200092, China. Electronic address: light_0315@126.com.
authors: Ang
authors: A
authors: Cui
authors: Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Kongjiang Road 1665, Shanghai, 200092, China. Electronic address: huxuguangxinhua@163.com.
authors: Xuguang
authors: X
authors: Hu
authors: Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Kongjiang Road 1665, Shanghai, 200092, China. Electronic address: longcuidr@126.com.
authors: Long
authors: L
authors: Cui
authors: Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Kongjiang Road 1665, Shanghai, 200092, China. Electronic address: nathanyang@hotmail.com.
authors: Yili
authors: Y
authors: Yang
authors: Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Kongjiang Road 1665, Shanghai, 200092, China. Electronic address: cyliu_eric@126.com.
authors: Chen-Ying
authors: CY
authors: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019898:Autocrine Communication; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D002955:Leucovorin / Q000627:therapeutic use; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D017211:Treatment Failure; D000097043:Interleukin-22
chemical_list: D000970:Antineoplastic Agents; D005472:Fluorouracil; D016209:Interleukin-8; D007378:Interleukins; D002955:Leucovorin; D009944:Organoplatinum Compounds; D050796:STAT3 Transcription Factor; D000097043:Interleukin-22; C494086:STAT3 protein, human
keywords: Chemoresistance; Interleukin 22; Interleukin 8; STAT3