Guo Lixia, Wang Jingyu, Zhang Ting, Yang Yanan
Thoracic Disease Research Unit, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Thoracic Disease Research Unit, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA; Developmental Therapeutics and Cell Biology Programs, Mayo Clinic Cancer Center, Mayo Clinic, Rochester, MN 55905, USA.
Biochem Biophys Rep. 2016 Jul;6:108-112. doi: 10.1016/j.bbrep.2016.03.010.
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. , 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.
磷脂酰肌醇蛋白聚糖-5(GPC5)属于蛋白聚糖的磷脂酰肌醇蛋白聚糖家族,该家族与从细胞增殖到形态发生的多种生理过程有关。然而,GPC5在人类癌症中的作用仍知之甚少。我们报告称,支气管上皮细胞中GPC5的敲低促进了非小细胞肺癌(NSCLC)细胞的非锚定依赖性细胞生长,而在NSCLC细胞中强制表达GPC5则抑制了这种生长。此外,GPC5的表达抑制了NSCLC细胞的异种移植肿瘤生长。此外,我们发现GPC5主要作为一种膜蛋白表达,其表达导致几种致癌受体酪氨酸激酶的磷酸化减少,包括在肺肿瘤发生中起关键作用的ERBB家族成员ERBB2和ERBB3。总体而言,我们的结果表明GPC5可能作为一种肿瘤抑制因子,激活GPC5的试剂可能对治疗NSCLC有用。