Abstract 3037: Cyr61/CCN1 regulates SHh through Notch signaling in pancreatic cancer cells

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Abstract Cyr61 (cysteine-rich 61)/CCN1, a member of the CCN family of growth factors that includes CTGF, NOV, WISP-1, WISP-2 and WISP-3, is associated with the development of various cancers. Our recent studies found Cyr61/CCN1 play a critical role in pancreatic carcinogenesis through the induction of EMT and stemness. Cyr61 mRNA and protein were detected in the early precursor lesions and their expression intensified with disease progression. However, the mode of action of CCN1 in the pancreatic carcinogenesis is unknown. In this study, we have shown that CCN1 regulates the expression of Sonic hedgehog (SHh), a lipid-modified secreted signaling protein, plays a critical role in pancreatic cancer development from Pan1N lesions to invasive growth of the disease. Moreover, we also found that SHh regulation by CCN1in pancreatic cancer cells is mediated through the regulation Notch1 signaling pathway. These extensive studies proposed that targeting Cyr61/CCN1 can provide a new treatment option for patients with pancreatic cancer as blocking CCN1 simultaneously two critical pathways (i.e., SHh and Notch1) associated with the development of the disease as well as drug resistence. (THIS WORK IS SUPPORTED BY VA MERIT GRANT TO SB). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3037. doi:1538-7445.AM2012-3037

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