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Protein Kinase C regulates the complex between cell membrane molecules in ovarian cancer
Institution:1. Izmir Biomedicine and Genome Center, 35340, İzmir, Turkey;2. Department of Chemistry, The Graduate School of Natural and Applied Sciences, Dokuz Eylul University, 35390, İzmir, Turkey;3. Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, 35340, İzmir, Turkey;4. Department of Chemistry, Division of Biochemistry, Faculty of Science, Dokuz Eylul University, 35390, İzmir, Turkey;1. Deparment of Chemistry and Chemical Processing Technologies, Mersin University, 33343, Mersin, Turkey;2. Deparment of Chemistry and Chemical Processing Technologies, Dicle University, 21280, Diyarbakır, Turkey;3. Food Processing Programme, Mersin University, 33343, Mersin, Turkey;4. Deparment of Chemistry and Chemical Processing Technologies, Siirt University, 56100, Siirt, Turkey;5. Chemistry Department, Sciences Faculty, Erciyes University, 38039, Kayseri, Turkey;6. Technology Research & Application Center (TAUM), Erciyes University, 38039, Kayseri, Turkey;1. Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran;2. Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;1. Swedish Centre for Resource Recovery, University of Borås, 501 90, Borås, Sweden;2. The Flemish Institute for Technological Research, VITO NV, Boeretang 200, B-2400, Mol, Belgium;3. Department of Chemical Engineering, Amirkabir University of Technology, 15875-4413, Tehran, Iran;4. Mixed Matrix Material Innovations BVBA, B-2160, Wommelgem, Belgium;1. Microbial Engineering Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, 110067, India;2. Systems Biology for Biofuel Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, 110067, India;3. DBT-ICGEB Centre for Advanced Bioenergy Research, International Centre for Genetic Engineering and Biotechnology, New Delhi, 110067, India;4. DBT-ICT Centre for Energy Biosciences, Institute of Chemical Technology, Mumbai 400019, India;1. College of Biology and Environmental Engineering, Zhejiang Shuren University, Hangzhou, 310015, PR China;2. Institute of Quality and Standard for Agriculture Products, Zhejiang Academy of Agricultural Science, Hangzhou, 310021, PR China;3. School of Food Science and Technology, Jiangnan University, Wuxi 214122, PR China
Abstract:The interactions between the integrated complex array of integral and peripheral cell adhesion molecules (CAMs) are tightly controlled by kinases such as Protein Kinase C (PKC) in response to changes in external or internal forces and/or signaling. Focusing on the complex of EpCAM-claudin-tetraspanin-driven ovarian cancer, we described a sequence of events by which role of PKCs located in the tetraspanin enriched microdomains affected on the interactions and performed immunoprecipitations in PKC activator and inhibitors-treated ovarian cancer cells and xenograft ovarian cancer mouse models. Activated PKC isoforms associated with tetraspanins and induced detectable changes in the claudin phosphorylation state. These results suggest that PKC targets claudin-4 ad -7. Phosphorylation, especially by PKC δ and η of claudins was important for the interactions between claudin-4, -7 and EpCAM. These results represent the direct evidence that phosphorylation of claudins by PKCs functions in the EpCAM-claudin-tetraspanin complex formation to allow these complexes to operate in ovarian cancer progression and metastasis in vitro and in vivo.
Keywords:Ovarian cancer  EpCAM  Claudins  Tetraspanins  Protein kinase C
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