CPI-17 drives oncogenic Ras signaling in human melanomas via Ezrin-Radixin-Moesin family proteins
| Autor: | Lars Björn Riecken, Ansgar Zoch, Ulrike Wiehl, Ulf Anderegg, Yan Cui, Ingmar Scholl, Mirjana Ziemer, Helen Morrison, Sabine Reichert, Christian Hagel |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Skin Neoplasms Time Factors Muscle Proteins medicine.disease_cause law.invention Mice Myosin-Light-Chain Phosphatase 0302 clinical medicine law CPI-17 Phosphoprotein Phosphatases Medicine Phosphorylation Neurofibromin 2 Mutation Melanoma Microfilament Proteins Intracellular Signaling Peptides and Proteins Gene Expression Regulation Neoplastic Cell Transformation Neoplastic ERM Oncology 030220 oncology & carcinogenesis RNA Interference Signal Transduction Protein family Transfection 03 medical and health sciences melanoma Animals Humans cancer Cell Proliferation business.industry Membrane Proteins Cancer medicine.disease Merlin (protein) Cytoskeletal Proteins 030104 developmental biology Immunology NIH 3T3 Cells ras Proteins Cancer research Suppressor business Carcinogenesis Ras HeLa Cells Priority Research Paper |
| Zdroj: | OncoTarget, 7:78242-78254 Oncotarget |
| Popis: | // Lars Bjorn Riecken 1 , Ansgar Zoch 1 , Ulrike Wiehl 1 , Sabine Reichert 1,2 , Ingmar Scholl 1 , Yan Cui 1 , Mirjana Ziemer 3 , Ulf Anderegg 3 , Christian Hagel 4 and Helen Morrison 1 1 Leibniz Institute on Aging, Fritz Lipmann Institute, Jena, Germany 2 Department of Cell and Developmental Biology, University College London, London, United Kingdom 3 Klinik und Poliklinik fur Dermatologie, Venerologie und Allergologie, Universitat Leipzig, Leipzig, Germany 4 Department of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Correspondence to: Helen Morrison, email: // Keywords : CPI-17, ERM, Ras, cancer, melanoma Received : January 14, 2016 Accepted : October 21, 2016 Published : October 26, 2016 Abstract Hyperactive Ras signaling has strong oncogenic effects causing several different forms of cancer. Hyperactivity is frequently induced by mutations within Ras itself, which account for up to 30% of all human cancers. In addition, hyperactive Ras signaling can also be triggered independent of Ras by either mutation or by misexpression of various upstream regulators and immediate downstream effectors. We have previously reported that C-kinase potentiated protein phosphatase-1 inhibitor of 17 kDa (CPI-17) can drive Ras activity and promote tumorigenic transformation by inhibition of the tumor suppressor Merlin. We now describe an additional element of this oncogenic mechanism in the form of the ezrin-radixin-moesin (ERM) protein family, which exhibits opposing roles in Ras activity control. Thus, CPI-17 drives Ras activity and tumorigenesis in a two-fold way; inactivation of the tumor suppressor merlin and activation of the growth promoting ERM family. The in vivo significance of this oncogenic switch is highlighted by demonstrating CPI-17’s involvement in human melanoma pathogenesis. |
| Databáze: | OpenAIRE |
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