The angiogenic factor CYR61 in breast cancer: molecular pathology and therapeutic perspectives.

in Endocrine-Related Cancer
Authors:
J A Menéndez Department of Medicine, Evanston Northwestern Healthcare Research Institute, 1001 University Place, Evanston, IL 60201, USA.

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I Mehmi Department of Medicine, Evanston Northwestern Healthcare Research Institute, 1001 University Place, Evanston, IL 60201, USA.

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D W Griggs Department of Medicine, Evanston Northwestern Healthcare Research Institute, 1001 University Place, Evanston, IL 60201, USA.

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R Lupu Department of Medicine, Evanston Northwestern Healthcare Research Institute, 1001 University Place, Evanston, IL 60201, USA.

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Volume/Issue:
Volume 10: Issue 2
Article Type:
Abstract
Page Range:
141–152
Online Publication Date:
Jun 2003
Free access

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CYR61 (CNN1), a member of the cysteine rich 61/connective tissue growth factor/nephroblastoma overexpressed (CYR61/CTFG/NOV) family of growth regulators (CNN), is a pro-angiogenic factor that mediates diverse roles in development, cell proliferation, and tumorigenesis. We have recently shown that CYR61 is overexpressed in invasive and metastatic human breast cancer cells. Accordingly, elevated levels of CYR61 in breast cancer are associated with more advanced disease. Unfortunately, the exact mechanisms by which CYR61 promotes an aggressive breast cancer phenotype are still largely unknown. This review examines the functional role of CYR61 in breast cancer disease, presenting evidence that CYR61 signaling may play a major role in estrogen- as well as growth factor-dependent breast cancer progression. We also emphasize the functional significance of the molecular connection of CYR61 and its integrin receptor alpha(v)beta(3) enhancing breast cancer aggressiveness. Moreover, we describe experimental evidence that establishes a novel role for CYR61 determining the protection of human breast cancer cells against chemotherapy-induced apoptosis through its interactions with the integrin receptor alpha(v)beta(3). All these findings delineate a new noteworthy function of a CYR61/alpha(v)beta(3) autocrine-paracrine signaling pathway within both angiogenesis and breast cancer progression, which would allow a dual anti-angiogenic and anti-tumor benefit with a single drug.

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Print ISSN:
1351-0088
Online ISSN:
1479-6821
Page(s):
12
Print Publication Date:
01 Jan 2003
Online Publication Date:
Jun 2003