A concerted HIF-1α/MT1-MMP signalling axis regulates the expression of the 3BP2 adaptor protein in hypoxic mesenchymal stromal cells.

ABSTRACT: Increased plasticity, migratory and immunosuppressive abilities characterize mesenchymal stromal cells (MSC) which enable them to be active participants in the development of hypoxic solid tumours. Our understanding of the oncogenic adaptation of MSC to hypoxia however lacks the identification and characterization of specific biomarkers. In this study, we assessed the hypoxic regulation of 3BP2/SH3BP2 (Abl SH3-binding protein 2), an immune response adaptor/scaffold protein which regulates leukocyte differentiation and motility. Gene silencing of 3BP2 abrogated MSC migration in response to hypoxic cues and generation of MSC stably expressing the transcription factor hypoxia inducible factor 1alpha (HIF-1α) resulted in increased endogenous 3BP2 expression as well as cell migration. Analysis

SUBMITTER: Proulx-Bonneau S 

PROVIDER: S-EPMC3124525 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature