PTPRS drives adaptive resistance to MEK/ERK inhibitors through SRC.

Autor:	Davis TB; Department of Surgery, University of Utah, Salt Lake City, UT 84132, USA., Yang M; Department of Surgery, University of Utah, Salt Lake City, UT 84132, USA., Wang H; Department of Surgery, University of Utah, Salt Lake City, UT 84132, USA., Lee C; Gibbs Cancer Center & Research Institute, Spartanburg, SC 29303, USA., Yeatman TJ; Department of Surgery, University of Utah, Salt Lake City, UT 84132, USA.; Cell Response and Regulation Program, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84132, USA.; Oncology Clinical Program, Intermountain Healthcare, Murray, UT 84107, USA., Pledger WJ; Department of Surgery, University of Utah, Salt Lake City, UT 84132, USA.; Cell Response and Regulation Program, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84132, USA.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2019 Nov 26; Vol. 10 (63), pp. 6768-6780. Date of Electronic Publication: 2019 Nov 26 (Print Publication: 2019).
DOI:	10.18632/oncotarget.27335
Abstrakt:	PTPRS is the most commonly mutated receptor tyrosine phosphatase in colorectal cancer (CRC). PTPRS has been shown to directly affect ERK and regulate its activation and nuclear localization. Here we identify that PTPRS may play a significant role in developing adaptive resistance to MEK/ERK inhibitors (MEKi/ERKi) through SRC activation. Moreover, we demonstrate a new clinical approach to averting adaptive resistance through the use of the SRC inhibitor, dasatinib. Our data suggest the potential for dasatinib to enhance the efficacy of MEKi and ERKi by preventing adaptive resistance pathways operating through SRC. Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.
Databáze:	MEDLINE
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