Transcriptional signatures of Ral GTPase are associated with aggressive clinicopathologic characteristics in human cancer.

Cancer Research
S C SmithD Theodorescu

Abstract

RalA and RalB are small GTPases that support malignant development and progression in experimental models of bladder, prostate, and squamous cancer. However, demonstration of their clinical relevance in human tumors remains lacking. Here, we developed tools to evaluate Ral protein expression, activation, and transcriptional output and evaluated their association with clinicopathologic parameters in common human tumor types. To evaluate the relevance of Ral activation and transcriptional output, we correlated RalA and RalB activation with the mutational status of key human bladder cancer genes. We also identified and evaluated a transcriptional signature of genes that correlates with depletion of RalA and RalB in vivo. The Ral transcriptional signature score, but not protein expression as evaluated by immunohistochemistry, predicted disease stage, progression to muscle invasion, and survival in human bladder cancers and metastatic and stem cell phenotypes in bladder cancer models. In prostate cancer, the Ral transcriptional signature score was associated with seminal vesicle invasion, androgen-independent progression, and reduced survival. In squamous cell carcinoma, this score was decreased in cancer tissues compared with norma...Continue Reading

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Citations

Jul 9, 2013·Experimental Cell Research·David F Kashatus
Apr 12, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hong WangDan Theodorescu
Jan 7, 2014·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Sunny GuinDan Theodorescu
May 15, 2015·BMC Systems Biology·Ricardo de Matos SimoesFrank Emmert-Streib
Jan 6, 2015·Acta Pharmacologica Sinica·Sunny Guin, Dan Theodorescu
Oct 28, 2016·Biochemical and Biophysical Research Communications·Richard Wong, Larry A Feig
Oct 21, 2016·Journal of Neuro-oncology·Kevin F GinnFaris Farassati
Nov 29, 2020·Communications Biology·Megan M TuDan Theodorescu
Aug 29, 2012·Cancer Research·Shibu ThomasDan Theodorescu
Oct 31, 2020·Cell Death & Disease·Hajrah KhawajaSandra Van Schaeybroeck

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