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Sonic advance: CCN1 regulates sonic hedgehog in pancreatic cancer
Authors:Andrew Leask
Affiliation:1. Department of Dentistry, Schulich School of Medicine and Dentistry, Dental Sciences Building, University of Western Ontario, London, ON, Canada, N6A 5C1
2. Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Dental Sciences Building, University of Western Ontario, London, ON, Canada, N6A 5C1
Abstract:Pancreatic ductal adenocarcinoma (PDAC) is the fifth leading cause of cancer internationally. As the precise molecular pathways that regulate pancreatic cancer are incompletely understood, appropriate targets for drug intervention remain elusive. It is being increasingly appreciated that the cellular microenvironment plays an important role in driving tumor growth and metastasis. CCN1, a member of the CCN family of secreted matricellular proteins, is overexpressed in pancreatic cancer, and may represent a novel target for therapy. Sonic hedgehog (SHh) is responsible for PDAC cell proliferation, epithelial-mesenchymal transition (EMT), maintenance of cancer stemness, migration, invasion, and metastatic growth; in a recent report, it was shown that CCN1 is a potent regulator of SHh expression via Notch-1. CCN1 activity was mediated, at least in part, through altering proteosome activity. These results suggest that CCN1 may be an ideal target for treating PDAC.
Keywords:CCN1   Pancreatic cancer   Sonic hedgehog   Notch   Microenvironment
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