气候变化领域集成服务门户(CCPortal): Interplay between desmoglein2 and hypoxia controls metastasis in breast cancer

CCPortal

DOI	10.1073/pnas.2014408118
	Interplay between desmoglein2 and hypoxia controls metastasis in breast cancer
	Chang P.-H.; Chen M.-C.; Tsai Y.-P.; Tan G.Y.T.; Hsu P.-H.; Jeng Y.-M.; Tsai Y.-F.; Yang M.-H.; Hwang-Verslues W.W.
发表日期	2021
ISSN	00278424
卷号	118 期号:3
英文摘要	Metastasis is the major cause of cancer death. An increased level of circulating tumor cells (CTCs), metastatic cancer cells that have intravasated into the circulatory system, is particularly associated with colonization of distant organs and poor prognosis. However, the key factors required for tumor cell dissemination and colonization remain elusive. We found that high expression of desmoglein2 (DSG2), a component of desmosome-mediated intercellular adhesion complexes, promoted tumor growth, increased the prevalence of CTC clusters, and facilitated distant organ colonization. The dynamic regulation of DSG2 by hypoxia was key to this process, as down-regulation of DSG2 in hypoxic regions of primary tumors led to elevated epithelial−mesenchymal transition (EMT) gene expression, allowing cells to detach from the primary tumor and undergo intravasation. Subsequent derepression of DSG2 after intravasation and release of hypoxic stress was associated with an increased ability to colonize distant organs. This dynamic regulation of DSG2 was mediated by Hypoxia-Induced Factor1α (HIF1α). In contrast to its more widely observed function to promote expression of hypoxia-inducible genes, HIF1α repressed DSG2 by recruitment of the polycomb repressive complex 2 components, EZH2 and SUZ12, to the DSG2 promoter in hypoxic cells. Consistent with our experimental data, DSG2 expression level correlated with poor prognosis and recurrence risk in breast cancer patients. Together, these results demonstrated the importance of DSG2 expression in metastasis and revealed a mechanism by which hypoxia drives metastasis. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Circulating tumor cells (CTCs) \| breast cancer \| metastasis \| desmoglein2 (DSG2) \| HIF1α
语种	英语
scopus关键词	desmoglein 2; hypoxia inducible factor 1alpha; transcription factor EZH2; animal experiment; animal model; animal tissue; Article; breast cancer; cancer patient; cancer prognosis; circulating tumor cell; controlled study; correlational study; down regulation; epithelial mesenchymal transition; female; gene; gene expression; human; human tissue; hypoxia; metastasis; mouse; nonhuman; prevalence; priority journal; protein expression; protein function; recurrence risk; tumor cell; tumor growth
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/180967
作者单位	Genomics Research Center, Academia Sinica, Taipei, 115, Taiwan; Asclepiumm Taiwan Co., Ltd, New Taipei City, 25160, Taiwan; Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung City, 20224, Taiwan; Department of Pathology, National Taiwan University Hospital, Taipei, 100, Taiwan; Department of Surgery, Taipei-Veterans General Hospital, Taipei City, 112, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, 112, Taiwan
推荐引用方式 GB/T 7714	Chang P.-H.,Chen M.-C.,Tsai Y.-P.,et al. Interplay between desmoglein2 and hypoxia controls metastasis in breast cancer[J],2021,118(3).
APA	Chang P.-H..,Chen M.-C..,Tsai Y.-P..,Tan G.Y.T..,Hsu P.-H..,...&Hwang-Verslues W.W..(2021).Interplay between desmoglein2 and hypoxia controls metastasis in breast cancer.Proceedings of the National Academy of Sciences of the United States of America,118(3).
MLA	Chang P.-H.,et al."Interplay between desmoglein2 and hypoxia controls metastasis in breast cancer".Proceedings of the National Academy of Sciences of the United States of America 118.3(2021).