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A Precision Strategy to Cure Renal Cell Carcinoma by Targeting Transglutaminase 2

1
Division of Cancer Biology, National Cancer Center, Goyang 10408, Korea
2
Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, ON K1N 6N5, Canada
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(7), 2493; https://doi.org/10.3390/ijms21072493
Received: 27 February 2020 / Revised: 29 March 2020 / Accepted: 1 April 2020 / Published: 3 April 2020
In a recent report, no significance of transglutaminase 2 (TGase 2) was noted in the analyses of expression differences between normal and clear cell renal cell carcinoma (ccRCC), although we found that knock down of TGase 2 induced significant p53-mediated cell death in ccRCC. Generally, to find effective therapeutic targets, we need to identify targets that belong specifically to a cancer phenotype that can be differentiated from a normal phenotype. Here, we offer precise reasons why TGase 2 may be the first therapeutic target for ccRCC, according to several lines of evidence. TGase 2 is negatively regulated by von Hippel-Lindau tumor suppressor protein (pVHL) and positively regulated by hypoxia-inducible factor 1-α (HIF-1α) in renal cell carcinoma (RCC). Therefore, most of ccRCC presents high level expression of TGase 2 because over 90% of ccRCC showed VHL inactivity through mutation and methylation. Cell death, angiogenesis and drug resistance were specifically regulated by TGase 2 through p53 depletion in ccRCC because over 90% of ccRCC express wild type p53, which is a cell death inducer as well as a HIF-1α suppressor. Although there have been no detailed studies of the physiological role of TGase 2 in multi-omics analyses of ccRCC, a life-long study of the physiological roles of TGase 2 led to the discovery of the first target as well as the first therapeutic treatment for ccRCC in the clinical field. View Full-Text
Keywords: clear cell renal cell carcinoma (ccRCC); transglutaminase 2 (TGase 2); p53; therapeutic target clear cell renal cell carcinoma (ccRCC); transglutaminase 2 (TGase 2); p53; therapeutic target
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Kim, S.-Y.; Keillor, J.W. A Precision Strategy to Cure Renal Cell Carcinoma by Targeting Transglutaminase 2. Int. J. Mol. Sci. 2020, 21, 2493.

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