| Literature DB >> 25670080 |
Samuel J Vidal1, Veronica Rodriguez-Bravo2, S Aidan Quinn3, Ruth Rodriguez-Barrueco4, Amaia Lujambio5, Estrelania Williams4, Xiaochen Sun6, Janis de la Iglesia-Vicente4, Albert Lee7, Ben Readhead8, Xintong Chen6, Matthew Galsky6, Berta Esteve4, Daniel P Petrylak9, Joel T Dudley8, Raul Rabadan7, Jose M Silva4, Yujin Hoshida6, Scott W Lowe5, Carlos Cordon-Cardo10, Josep Domingo-Domenech11.
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.Entities:
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Year: 2015 PMID： 25670080 PMCID： PMC4356948 DOI： 10.1016/j.ccell.2014.11.013
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743