分类: 生物学 >> 生物医药 提交时间: 2017-05-10
摘要: The von Hippel-Lindau (VHL) tumor suppressor gene regulates extracellular matrix deposition. InVHLnegative renal cancer cells, VHL(-), the lack of fibronectin matrix assembly is thought to promote and maintain tumor angiogenesis allowing vessels to infiltrate tumors. Therefore, and considering the importance of this process in tumor growth, we aimed to study why VHL(-) renal cancer cells fail to form a proper extracellular matrix. Our results showed that VHL(-) cells were not defective in fibronectin production and that the fibronectin produced by these cells was equally functional in promoting cell adhesion and matrix assembly as that produced by VHL(-) cells. We have previously reported that VHL(-) cells fail to form beta 1 integrin fibrillar adhesions and have a diminished organization of actin stress fibers; therefore, we aimed to study if the small GTPase family is involved in this process. We found that activation of the RhoA GTPase was defective in VHL(-) cells, and this was possibly mediated by an increased activation of its inhibitor, p190RhoGAP. Additionally, the expression of constitutively active RhoA in VHL(-) cells resulted in formation of a fibronectin matrix. These results strongly suggest an important role for RhoA in some of the defects observed in renal cancer cells.
分类: 生物学 >> 生态学 提交时间: 2017-11-17
摘要: From the (a)CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China, and Guangzhou Medical University, Guangzhou 511436, China, (b)CAS Key Laboratory of Regenerative Biology and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China, (c)Laboratory of RNA, Chromatin, and Human Disease, CAS Key Laboratory of Regenerative Biology and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China, (d)Cardiology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China, (e)Hong Kong-Guangdong Stem Cell and Regenerative Medicine Research Centre, The University of Hong Kong and Guangzhou Institutes of Biomedicine and Health, Hong Kong SAR, China, (f)Department of Ophthalmology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China, (g)State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangdong Provincial Research Center for Liver Fibrosis, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital and (h)Biomedical Research Center, Southern Medical University, Guangzhou 510515, China, (i)Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, (j)National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Unit and Centre for Liver Research, and (k)Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom, (l)Cambridge Institute for Medical Research, Wellcome Trust/Medical Research Council (MRC) Building, Cambridge CB2 0XY, United Kingdom, mDepartment of Clinical Biochemistry Unit, Queen Mary Hospital, Hong Kong SAR, China, (n)Department of Medicine, University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, Guangdong, China, and (o)Laboratory of Metabolism and Cell Fate, CAS Key Laboratory of Regenerative Biology and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, Guangdong, China