Integrins are heterodimeric transmembrane receptors, consisting of α and β subunits, that are non-covalently associated they physically link the ECM to the intracellular actin cytoskeleton but are also able to transduce signals bidirectionally across the plasma membrane. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.Īdhesion of cells to extracellular matrix (ECM) is primarily mediated by integrins and is crucial for cell growth and survival. Languino, the corresponding author, is an editorial board member for PLOS ONE. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: Dr. This project is also funded, in part, under a Commonwealth University Research Enhancement Program grant with the Pennsylvania Department of Health (H.R.). This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: Contract grant sponsor: NIH Contract grant number: R01 CA-89720 and CA-109874 (to LRL), P01 CA-140043 (to LRL) American Cancer Society (ACS)-IRG-08-060-04 (to AS) Contract grant sponsor: Pennsylvania Department of Health. Received: JAccepted: AugPublished: October 9, 2013Ĭopyright: © 2013 Sayeed et al. PLoS ONE 8(10):Įditor: Natasha Kyprianou, University of Kentucky College of Medicine, United States of America Our results reveal a crucial mechanistic role for the α 5β 1 integrin, downstream of IGF-IR, in regulating cancer growth.Ĭitation: Sayeed A, Fedele C, Trerotola M, Ganguly KK, Languino LR (2013) IGF-IR Promotes Prostate Cancer Growth by Stabilizing α 5β 1 Integrin Protein Levels. The α 5 subunit, one of the binding partners of β 1, is also downregulated along with β 1 upon IGF-IR knockdown while no change is observed in the expression of the α 2, α 3, α 4, α 6 and α 7 subunits. We demonstrate that IGF-IR stabilizes the β 1 subunit by protecting it from proteasomal degradation. This appears to be due to the lack of interaction between the β 1 cytoplasmic domain and IGF-IR. Exogenous expression of a CD4 - β 1 integrin cytoplasmic domain chimera does not interfere with such regulation and fails to stabilize β 1 integrin expression in the absence of IGF-IR. We demonstrate that β 1 integrin regulation by IGF-IR does not occur at the mRNA level. Here we report that IGF-IR is crucial for PrCa cell growth and that β 1 integrins contribute to the regulation of proliferation by IGF-IR. We have dissected the mechanism through which IGF-IR regulates β 1 integrin expression in PrCa. Furthermore, we have recently reported that IGF-IR regulates the expression of β 1 integrins in PrCa cells. We have previously demonstrated that β 1 integrins regulate anchorage-independent growth of prostate cancer (PrCa) cells by regulating IGF-IR expression and androgen receptor-mediated transcriptional functions. The type 1 insulin-like growth factor receptor (IGF-IR) mediates tumor cell growth, adhesion and inhibition of apoptosis in several types of cancer. They also mediate signal transduction to regulate cell proliferation and survival. Integrins are transmembrane receptors that bind extracellular matrix proteins and enable cell adhesion and cytoskeletal organization. Dynamic crosstalk between growth factor receptors, cell adhesion molecules and extracellular matrix is essential for cancer cell migration and invasion.
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