The matrix protein CCN1/CYR61 is required for α(V)β5-mediated cancer cell migration.

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 α(V)β5 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 α(V)β5 integrin. Further, we investigated whether tumour cell-secreted CYR61 can facilitate cell migration by interacting with the α(V)β5 integrin. Using tumour cell lines with low, intermediate and high CYR61 expression and their isogenic variants as a cellular model, we determined that integrin α(V)β5 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 α(V)β5 integrin as proteins that cooperate to mediate cancer cell migration.