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Glypican-5 is a tumor suppressor in non-small cell lung cancer cells
Authors:Lixia Guo  Jingyu Wang  Ting Zhang  Yanan Yang
Institution:1. Thoracic Disease Research Unit, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA;2. Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA;3. Developmental Therapeutics and Cell Biology Programs, Mayo Clinic Cancer Center, Mayo Clinic, Rochester, MN 55905, USA
Abstract:Glypican-5 (GPC5) belongs to the glypican family of proteoglycans that have been implicated in a variety of physiological processes, ranging from cell proliferation to morphogenesis. However, the role of GPC5 in human cancer remains poorly understood. We report that knockdown of GPC5 in bronchial epithelial cells promoted, and forced expression of GPC5 in non-small lung cancer (NSCLC) cells suppressed, the anchorage-independent cell growth. In vivo, expression of GPC5 inhibited xenograft tumor growth of NSCLC cells. Furthermore, we found that GPC5 was expressed predominantly as a membrane protein, and its expression led to diminished phosphorylation of several oncogenic receptor tyrosine kinases, including the ERBB family members ERBB2 and ERBB3, which play critical roles in lung tumorigenesis. Collectively, our results suggest that GPC5 may act as a tumor suppressor, and reagents that activate GPC5 may be useful for treating NSCLC.
Keywords:Glypican-5  Cell signaling  Tumor suppressor  Lung cancer
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