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

Samuel J. Vidal, Veronica Rodriguez-Bravo, S. Aidan Quinn, Ruth Rodriguez-Barrueco, Amaia Lujambio, Estrelania Williams, Xiaochen Sun, Janis delaIglesia-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-CardoJosep Domingo-Domenech

Research output: Contribution to journalArticlepeer-review


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 byGATA2. 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.

Original languageEnglish (US)
Pages (from-to)223-239
Number of pages17
JournalCancer cell
Issue number2
StatePublished - Feb 9 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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