Journal article

PtdIns(3,4,5)P-3-dependent Rac exchanger 1 (P-Rex1) promotes mammary tumor initiation and metastasis

Nuthasuda Srijakotre, Heng-jia Liu, Max Nobis, Joey Man, Hon Yan Kelvin Yip, Antonella Papa, Helen E Abud, Kurt I Anderson, Heidi CE Welch, Tony Tiganis, Paul Timpson, Catriona A McLean, Lisa M Ooms, Christina A Mitchell

Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2020

Abstract

The Rac-GEF, P-Rex1, activates Rac1 signaling downstream of G protein-coupled receptors and PI3K. Increased P-Rex1 expression promotes melanoma progression; however, its role in breast cancer is complex, with differing reports of the effect of its expression on disease outcome. To address this we analyzed human databases, undertook gene array expression analysis, and generated unique murine models of P-Rex1 gain or loss of function. Analysis of PREX1 mRNA expression in breast cancer cDNA arrays and a METABRIC cohort revealed that higher PREX1 mRNA in ER+ve/luminal tumors was associated with poor outcome in luminal B cancers. Prex1 deletion in MMTV-neu or MMTV-PyMT mice reduced Rac1 activatio..

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Grants

Awarded by National Health and Medical Research Council


Funding Acknowledgements

This study utilized the Monash Micro Imaging Facility and Monash Histology Platform (Monash University). We acknowledge the resources, facilities, and scientific and technical assistance of the Monash Biomedicine Discovery Institute Organoid Program (Victoria, Australia). We thank Professor Jane Visvader for the MMTV-neu mice. This work was supported by a National Health and Medical Research Council grant (APP1104614).