A Targetable GATA2-IGF2 Axis Confers Aggressiveness in Lethal Prostate Cancer

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2015 Feb 12

PMID 25670080

Citations 83

Authors

Samuel J Vidal

Veronica Rodriguez-Bravo

S Aidan Quinn

Ruth Rodriguez-Barrueco

Amaia Lujambio

Estrelania Williams

Xiaochen Sun

Janis de la Iglesia-Vicente

Albert Lee

Ben Readhead

Xintong Chen

Matthew Galsky

Berta Esteve

Daniel P Petrylak

Joel T Dudley

Raul Rabadan

Jose M Silva

Yujin Hoshida

Scott W Lowe

Carlos Cordon-Cardo

Josep Domingo-Domenech

Affiliations

Soon will be listed here.

Abstract

Elucidating the determinants of aggressiveness in lethal prostate cancer may stimulate therapeutic strategies that improve clinical outcomes. We used experimental models and clinical databases to identify GATA2 as a regulator of chemotherapy resistance and tumorigenicity in this context. Mechanistically, direct upregulation of the growth hormone IGF2 emerged as a mediator of the aggressive properties regulated by GATA2. IGF2 in turn activated IGF1R and INSR as well as a downstream polykinase program. The characterization of this axis prompted a combination strategy whereby dual IGF1R/INSR inhibition restored the efficacy of chemotherapy and improved survival in preclinical models. These studies reveal a GATA2-IGF2 aggressiveness axis in lethal prostate cancer and identify a therapeutic opportunity in this challenging disease.

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