气候变化领域集成服务门户(CCPortal): Tetraspanin 6 is a regulator of carcinogenesis in colorectal cancer

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DOI	10.1073/pnas.2011411118
	Tetraspanin 6 is a regulator of carcinogenesis in colorectal cancer
	Andrijes R.; Hejmadi R.K.; Pugh M.; Rajesh S.; Novitskaya V.; Ibrahim M.; Overduin M.; Tselepis C.; Middleton G.W.; Gyorffy B.; Beggs A.D.; Berditchevski F.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:39
英文摘要	Early stages of colorectal cancer (CRC) development are characterized by a complex rewiring of transcriptional networks resulting in changes in the expression of multiple genes. Here, we demonstrate that the deletion of a poorly studied tetraspanin protein Tspan6 in Apcmin/+ mice, a well-established model for premalignant CRC, resulted in increased incidence of adenoma formation and tumor size. We demonstrate that the effect of Tspan6 deletion results in the activation of EGF-dependent signaling pathways through increased production of the transmembrane form of TGF-α (tmTGF-α) associated with extracellular vesicles. This pathway is modulated by an adaptor protein syntenin-1, which physically links Tspan6 and tmTGF-α. In support of this, the expression of Tspan6 is frequently decreased or lost in CRC, and this correlates with poor survival. Furthermore, the analysis of samples from the epidermal growth factor receptor (EGFR)-targeting clinical trial (COIN trial) has shown that the expression of Tspan6 in CRC correlated with better patient responses to EGFR-targeted therapy involving Cetuximab. Importantly, Tspan6- positive patients with tumors in the proximal colon (right-sided) and those with KRAS mutations had a better response to Cetuximab than the patients that expressed low Tspan6 levels. These results identify Tspan6 as a regulator of CRC development and a potential predictive marker for EGFR-targeted therapies in CRC beyond RAS pathway mutations. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	APCmin; Colorectal cancer; EGFR; Tetraspanin; TGF alpha
语种	英语
scopus关键词	cetuximab; EGFR protein, human; epidermal growth factor receptor; immunological antineoplastic agent; tetraspanin; tetraspanin 6 protein, mouse; TSPAN6 protein, human; tumor marker; animal; apoptosis; C57BL mouse; cell proliferation; colorectal tumor; gene expression regulation; genetics; human; knockout mouse; metabolism; mouse; pathology; physiology; prognosis; survival rate; tumor cell culture; Animals; Antineoplastic Agents, Immunological; Apoptosis; Biomarkers, Tumor; Cell Proliferation; Cetuximab; Colorectal Neoplasms; ErbB Receptors; Gene Expression Regulation, Neoplastic; Humans; Mice; Mice, Inbred C57BL; Mice, Knockout; Prognosis; Survival Rate; Tetraspanins; Tumor Cells, Cultured
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251015
作者单位	Institute of Cancer and Genomic Sciences, The University of Birmingham, Birmingham, B15 2TT, United Kingdom; University Hospitals Birmingham, National Health Service Foundation Trust, Birmingham, B15 2TH, United Kingdom; South Egypt Cancer Institute, Assiut University, Assiut, 71515, Egypt; Department of Bioinformatics, Semmelweis University, Budapest, 1094, Hungary; 2nd Department of Paediatrics, Semmelweis University, Budapest, 1094, Hungary; TTK Cancer Biomarker Research Group, Budapest, 1117, Hungary
推荐引用方式 GB/T 7714	Andrijes R.,Hejmadi R.K.,Pugh M.,et al. Tetraspanin 6 is a regulator of carcinogenesis in colorectal cancer[J],2021,118(39).
APA	Andrijes R..,Hejmadi R.K..,Pugh M..,Rajesh S..,Novitskaya V..,...&Berditchevski F..(2021).Tetraspanin 6 is a regulator of carcinogenesis in colorectal cancer.Proceedings of the National Academy of Sciences of the United States of America,118(39).
MLA	Andrijes R.,et al."Tetraspanin 6 is a regulator of carcinogenesis in colorectal cancer".Proceedings of the National Academy of Sciences of the United States of America 118.39(2021).