Tissue factor/factor VIIa induces cell survival and gene transcription by transactivation of the insulin-like growth factor 1 receptor

Thrombosis and Haemostasis
Mikael AbergAgneta Siegbahn

Abstract

The insulin-like growth factor 1 receptor (IGF-1R) is known to promote survival and has also been implicated in the pathogenesis of several disease states, including cardiovascular disorders and cancer. Recently, we showed that binding of coagulation factor VIIa (FVIIa) to its receptor tissue factor (TF) protects cancer cells from TNF-related apoptosis inducing ligand (TRAIL)-induced apoptosis. Here we present evidence that this biological function of TF/FVIIa is dependent on the IGF-1R. IGF-1R inhibitors AG1024 and PPP as well as siRNA-mediated downregulation of IGF-1R, abolished the TF/FVIIa-mediated protection against TRAIL-induced apoptosis. Moreover, FVIIa rapidly induced a time- and concentration-dependent tyrosine phosphorylation of the IGF-1R in MDA-MB-231 breast cancer cells and in primary human monocytes, an event that was accompanied by IGF-1R chromatin binding and gene transcription. We hereby present novel evidence of a cross-talk between the coagulation and IGF-1R signalling systems, and propose that the IGF-1R is a key player in mediating TF/FVIIa-induced cell survival.

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Citations

May 23, 2015·Thrombosis and Haemostasis·C Arnold SpekKeren S Borensztajn
Sep 8, 2016·Biochimica Et Biophysica Acta·Camille EttelaieAnthony Maraveyas
Jul 22, 2018·Journal of Thrombosis and Haemostasis : JTH·H ZelayaW Ruf
May 28, 2020·Apoptosis : an International Journal on Programmed Cell Death·Mikael ÅbergAgneta Siegbahn
Jul 16, 2020·Journal of Hematology & Oncology·Dusten Unruh, Craig Horbinski
Oct 28, 2019·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Pete T KinnunenTeemu J Murtola

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