Search

Search Results

1 results found. Results per page: [ 20 ][ 40 ][ 60 ][ 80 ][ 100 ][ 200 ][ 300 ]

Sort by: [ Publication Date ][ Score ]

Year of publication: [ 2025 ][ 2024 ][ 2023 ][ 2022 ][ 2021 ][ 2020 ][ 2019 ][ 2018 ][ 2017 ][ 2016 ][ 2015 ][ 2014 ][ 2013 ][ 2012 ][ 2011 ][ 2010 ][ 2009 ][ Any ]

Direction: [ Desc ][ Asc ]

• Research Perspective Volume 7, Issue 7 pp 469-474

  Heterotrimeric G proteins as emerging targets for network based therapy in cancer: End of a long futile campaign striking heads of a Hydra

  Relevance score: 18.362846

  Pradipta Ghosh

  Keywords: GIV, Girdin, growth factor receptor tyrosine kinases, cancer metastasis, G protein -coupled receptors, heterotrimeric G proteins

  Published in Aging on July 20, 2015

  Show abstract
  Hide abstract

  Most common diseases, e.g., cancer are driven by not one, but multiple cell surface receptors that trigger and sustain a pathologic signaling network. The largest fraction of therapeutic agents that target individual receptors/pathways eventually fail due to the emergence of compensatory mechanisms that reestablish the pathologic network. Recently, a rapidly emerging paradigm has revealed GIV/Girdin as a central platform for receptor cross-talk which integrates signals downstream of a myriad of cell surface receptors, and modulates several key pathways within downstream signaling network, all via non-canonical activation of trimeric G proteins. Unlike canonical signal transduction via G proteins, which is spatially and temporally restricted, the temporal and spatial features of non-canonical activation of G protein via GIV is unusually unrestricted. Consequently, the GIV●G protein interface serves as a central hub allowing for control over several pathways within the pathologic signaling network, all at once. The relevance of this new paradigm in cancer and other disease states and the pros and cons of targeting the GIV●G protein interface are discussed

  

  Schematic showing the diverse classes of receptors (upper half) which sense a variety of chemical signals, that converge on GIV. Lower part shows the consequence of non-canonical transactivation of G proteins by GIV (when GIV-GEF is functionally intact or turned "ON") on the multitude of downstream pathways within the signaling network. Green = enhancement; Red = suppression. Shown in the middle are three known ways to either inhibit (PKCθ selectively phosphoinhibits GIV-GEF [27]; SHP-1 dephosphorylates tyrosine-phosphorylated GIV [30]) or activate (CDK5 phosphoactivates GIV-GEF [37]) GIV-dependent signaling.

  
  
  

  

  Schematic summarizing the variety of solid tumors in which elevated expression of GIV/Girdin in tumor cells has been linked to its role in imparting stemness, invasiveness, prometastatic and anti-apoptotic signaling, aggressiveness and poor clinical outcome has been studied.