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The matrix protein CCN1/CYR61 is required for αVβ5‐mediated cancer cell migration
Authors:Jana Jandova  Tracey E Beyer  Emmanuelle J Meuillet  George S Watts
Institution:1. Department of Medicine, Dermatology Division, University of Arizona, , Tucson, AZ 85724 USA;2. The University of Arizona Cancer Center, , Tucson, AZ 85721 USA;3. Department of Nutritional Sciences, College of Agriculture and Life Sciences, The University of Arizona, , Tucson, AZ 85721 USA;4. Department of Molecular and Cellular Biology, College of Sciences, The University of Arizona, , Tucson, AZ 85721 USA;5. Department of Pharmacology and Toxicology, The University of Arizona, , Tucson, AZ 85721 USA
Abstract:CYR61 is one of the six proteins of the CCN family of proteins known to play diverse roles in angiogenesis, cellular proliferation, survival, migration and wound healing. However, the specific function of CYR61 in cancer is unclear, and the literature remains controversial. We used quantitative real‐time PCR to establish the expression profile of CYR61 and integrin αVβ5 in three non–small cell lung cancer, five colorectal cancer, one breast cancer and one oesophageal squamous carcinoma cell lines. We showed that the levels of CYR61 were significantly increased in oesophageal squamous carcinoma cell line along with the enhanced levels of αVβ5 integrin. Further, we investigated whether tumour cell–secreted CYR61 can facilitate cell migration by interacting with the αVβ5 integrin. Using tumour cell lines with low, intermediate and high CYR61 expression and their isogenic variants as a cellular model, we determined that integrin αVβ5 expressed on these tumour cells is required for cell migration. Moreover, we showed that the modulation of expression levels of CYR61 in these cancer cells affected their capacity for migration. These results represent an advance to the understanding of the role of CYR61 and αvβ5 integrin as proteins that cooperate to mediate cancer cell migration. Copyright © 2012 John Wiley & Sons, Ltd.
Keywords:CYR61  stable overexpression  stable knockdown  integrin α    5  migration
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