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-Cardo; Josep Domingo-Domenech

doi:10.1016/j.ccell.2014.11.013

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 journal › Article › peer-review

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 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 language	English (US)
Pages (from-to)	223-239
Number of pages	17
Journal	Cancer cell
Volume	27
Issue number	2
DOIs	https://doi.org/10.1016/j.ccell.2014.11.013
State	Published - Feb 9 2015

ASJC Scopus subject areas

Oncology
Cancer Research

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Vidal, S. J., Rodriguez-Bravo, V., Quinn, S. A., Rodriguez-Barrueco, R., Lujambio, A., Williams, E., Sun, X., delaIglesia-Vicente, J., Lee, A., Readhead, B., Chen, X., Galsky, M., Esteve, B., Petrylak, D. P., Dudley, J. T., Rabadan, R., Silva, J. M., Hoshida, Y., Lowe, S. W., ... Domingo-Domenech, J. (2015). A Targetable GATA2-IGF2 Axis Confers Aggressiveness in Lethal Prostate Cancer. Cancer cell, 27(2), 223-239. https://doi.org/10.1016/j.ccell.2014.11.013

Vidal, SJ, Rodriguez-Bravo, V, Quinn, SA, Rodriguez-Barrueco, R, Lujambio, A, Williams, E, Sun, X, delaIglesia-Vicente, J, Lee, A, Readhead, B, Chen, X, Galsky, M, Esteve, B, Petrylak, DP, Dudley, JT, Rabadan, R, Silva, JM, Hoshida, Y, Lowe, SW, Cordon-Cardo, C & Domingo-Domenech, J 2015, 'A Targetable GATA2-IGF2 Axis Confers Aggressiveness in Lethal Prostate Cancer', Cancer cell, vol. 27, no. 2, pp. 223-239. https://doi.org/10.1016/j.ccell.2014.11.013

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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 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.",

author = "Vidal, {Samuel J.} and Veronica Rodriguez-Bravo and Quinn, {S. Aidan} and Ruth Rodriguez-Barrueco and Amaia Lujambio and Estrelania Williams and Xiaochen Sun and Janis delaIglesia-Vicente and Albert Lee and Ben Readhead and Xintong Chen and Matthew Galsky and Berta Esteve and Petrylak, {Daniel P.} and Dudley, {Joel T.} and Raul Rabadan and Silva, {Jose M.} and Yujin Hoshida and Lowe, {Scott W.} and Carlos Cordon-Cardo and Josep Domingo-Domenech",

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AU - Rodriguez-Bravo, Veronica

AU - Quinn, S. Aidan

AU - Rodriguez-Barrueco, Ruth

AU - Lujambio, Amaia

AU - Williams, Estrelania

AU - Sun, Xiaochen

AU - delaIglesia-Vicente, Janis

AU - Lee, Albert

AU - Readhead, Ben

AU - Chen, Xintong

AU - Galsky, Matthew

AU - Esteve, Berta

AU - Petrylak, Daniel P.

AU - Dudley, Joel T.

AU - Rabadan, Raul

AU - Silva, Jose M.

AU - Hoshida, Yujin

AU - Lowe, Scott W.

AU - Cordon-Cardo, Carlos

AU - Domingo-Domenech, Josep

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

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