Polymeric Immunoglobulin Receptor Promotes Tumor Growth in Hepatocellular Carcinoma

doi:10.1002/hep.29036

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	Polymeric Immunoglobulin Receptor Promotes Tumor Growth in Hepatocellular Carcinoma
	Yue, Xihua 2; Ai, Jing2 ; Xu, Yang 3,4; Chen, Yi2 ; Huang, Min2 ; Yang, Xinying 2; Hu, Bo 3,4; Zhang, Haotian 2; He, Changxi 2; Yang, Xinrong 3,4
刊名	HEPATOLOGY
	2017-06
卷号	65 期号:6 页码:1948-1962
ISSN号	0270-9139
DOI	10.1002/hep.29036
文献子类	Article
英文摘要	Deregulation of the immune system is believed to contribute to cancer malignancy, which has led to recent therapeutic breakthroughs facilitating antitumor immunity. In a malignant setting, immunoglobulin receptors, which are fundamental components of the human immune system, fulfill paradoxical roles in cancer pathogenesis. This study describes a previously unrecognized pro-oncogenic function of polymeric immunoglobulin receptor (pIgR) in the promotion of cell transformation and proliferation. Mechanistically, pIgR overexpression is associated with YES proto-oncogene 1, Src family tyrosine kinase (Yes) activation, which is required for pIgR-induced oncogenic growth. Specifically, pIgR activates the Yes-DNAX-activating protein of 12 kDa-spleen tyrosine kinase-Rac1/CDC42-MEK (extracellular signal-regulated kinase kinase)/ERK (extracellular signal-regulated kinase) cascade in an immunoreceptor tyrosine-based activating motif (ITAM)-dependent manner to promote cell transformation and tumor growth, although pIgR itself does not contain an ITAM sequence. Additionally, the combination of pIgR and phosphorylated Yes (p-Yes) levels serves as a prognostic biomarker for hepatitis B surface antigen-positive and early-stage hepatocellular carcinoma (HCC) patients. Moreover, pharmacological targeting of MEK/ERK or Yes represents a therapeutic option for the subgroup of patients with pIgR/p-Yes-positive HCC based on our results with both cancer cell-line-based xenografts and primary patient-derived xenografts. Conclusion: Our findings reveal the molecular mechanism by which pIgR promotes cancer malignancy, suggest the clinical potential of targeting this pathway in HCC, and provide new insight into the oncogenic role of immunoglobulin receptors.
资助项目	National Program on Key Basic Research Project of China[2012CB910704] ; National Natural Science Foundation of China[91229205] ; National Natural Science Foundation of China[81473243] ; National Natural Science Foundation of China[81321092] ; National Natural Science Foundation of China[81572884] ; National Natural Science Foundation of China[81372317] ; "Personalized Medicines-Molecular Signature-based Drug Discovery and Development", Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020000] ; NSFC-Shandong Joint Fund for Marine Science Research Centers[U1406402] ; Youth Innovation Promotion Association[2013189]
WOS关键词	TYROSINE KINASE ; FC-RECEPTORS ; IMMUNE-RESPONSES ; EPITHELIAL-CELLS ; MEK INHIBITION ; COMBINED BRAF ; TRANSCYTOSIS ; DASATINIB ; MELANOMA ; INFLAMMATION
WOS研究方向	Gastroenterology & Hepatology
语种	英语
出版者	WILEY
WOS记录号	WOS:000401608900017
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272650]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Fan, Jia; Ding, Jian; Geng, Meiyu
作者单位	1.Fudan Univ, Inst Biomed Sci, Shanghai, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; 3.Fudan Univ, Liver Canc Inst, Zhongshan Hosp, Dept Liver Surg, 136 Yi Xue Yuan Rd, Shanghai 200032, Peoples R China; 4.Minist Educ, Key Lab Carcinogenesis & Canc Invas, Shanghai, Peoples R China; 5.Second Mil Med Univ, Eastern Hepatobiliary Surg Inst, Int Cooperat Lab Signal Transduct, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Yue, Xihua,Ai, Jing,Xu, Yang,et al. Polymeric Immunoglobulin Receptor Promotes Tumor Growth in Hepatocellular Carcinoma[J]. HEPATOLOGY,2017,65(6):1948-1962.
APA	Yue, Xihua.,Ai, Jing.,Xu, Yang.,Chen, Yi.,Huang, Min.,...&Geng, Meiyu.(2017).Polymeric Immunoglobulin Receptor Promotes Tumor Growth in Hepatocellular Carcinoma.HEPATOLOGY,65(6),1948-1962.
MLA	Yue, Xihua,et al."Polymeric Immunoglobulin Receptor Promotes Tumor Growth in Hepatocellular Carcinoma".HEPATOLOGY 65.6(2017):1948-1962.