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Caveolin-1 Contributes To Regulation Of Radiation Survival Via The B1 Integrin/AKT Signaling Axis
The integral membrane protein Caveolin-1 forms small invaginations of the plasma membrane, so-called caveolae, for serving in endo-exocytosis and is involved in regulating signaling from integrins and receptor-tyrosine kinases. Both, integrins and receptor-tyrosine kinases, are considered to confer radioresistance and chemoresistance of tumours. Integrins are responsible for interactions of cells with their surrounding extracellular matrix, transmit extracellular signals to control survival, proliferation or apoptosis, and have been demonstrated to transduce prosurvival signals via the cytoplasmic protein kinase AKT. The aim of this study was to evaluate the distinct role of Caveolin-1 in radiation survival of human pancreatic tumor cells and its putative interaction with the widely expressed ß1 integrin using a three-dimensional (3D) cell culture model, which mimics physiological growth conditions in contrast to the conventional 2D cell culture.
Caveolin-1 overexpressing or Caveolin-1 siRNAtransfected pancreatic tumor cells were grown in a 3D laminin-rich extracellular matrix, irradiated (0-6 Gy, X-rays) and subjected to 3D clonogenic assays. The potential involvement of a range of signaling proteins in regulating cellular radiation survival were analyzed by Western blotting, immunoprecipitation and intracellular tracking of Caveolin-1-GFPand fluorochrome-labeled monoclonal anti-ß1 integrin antibodies.
Overexpression of Caveolin-1 improved clonogenic radiation survival of 3D grown cell lines while siRNA-mediated Caveolin-1 knockdown resulted in significantly (p
Caveolin-1 contribuie la Regulamentul de radiaþii de supravieþuire, prin intermediul B1 Integrin / AKT axa de semnalizare - Caveolin-1 Contributes To Regulation Of Radiation Survival Via The B1 Integrin/AKT Signaling Axis - articole medicale engleza - startsanatate
