PTPRS drives adaptive resistance to MEK/ERK inhibitors through SRC

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 inhibito...

Descripción completa

Detalles Bibliográficos
Autores principales: Davis, Thomas B., Yang, Mingli, Wang, Heiman, Lee, Changgong, Yeatman, Timothy J., Pledger, W. Jack
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2019
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887575/
https://www.ncbi.nlm.nih.gov/pubmed/31827720
http://dx.doi.org/10.18632/oncotarget.27335
_version_ 1783475047508213760
author Davis, Thomas B.
Yang, Mingli
Wang, Heiman
Lee, Changgong
Yeatman, Timothy J.
Pledger, W. Jack
author_facet Davis, Thomas B.
Yang, Mingli
Wang, Heiman
Lee, Changgong
Yeatman, Timothy J.
Pledger, W. Jack
author_sort Davis, Thomas B.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6887575
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-68875752019-12-11 PTPRS drives adaptive resistance to MEK/ERK inhibitors through SRC Davis, Thomas B. Yang, Mingli Wang, Heiman Lee, Changgong Yeatman, Timothy J. Pledger, W. Jack Oncotarget Research Paper 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. Impact Journals LLC 2019-11-26 /pmc/articles/PMC6887575/ /pubmed/31827720 http://dx.doi.org/10.18632/oncotarget.27335 Text en http://creativecommons.org/licenses/by/3.0/ Copyright: Davis et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Davis, Thomas B.
Yang, Mingli
Wang, Heiman
Lee, Changgong
Yeatman, Timothy J.
Pledger, W. Jack
PTPRS drives adaptive resistance to MEK/ERK inhibitors through SRC
title PTPRS drives adaptive resistance to MEK/ERK inhibitors through SRC
title_full PTPRS drives adaptive resistance to MEK/ERK inhibitors through SRC
title_fullStr PTPRS drives adaptive resistance to MEK/ERK inhibitors through SRC
title_full_unstemmed PTPRS drives adaptive resistance to MEK/ERK inhibitors through SRC
title_short PTPRS drives adaptive resistance to MEK/ERK inhibitors through SRC
title_sort ptprs drives adaptive resistance to mek/erk inhibitors through src
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887575/
https://www.ncbi.nlm.nih.gov/pubmed/31827720
http://dx.doi.org/10.18632/oncotarget.27335
work_keys_str_mv AT davisthomasb ptprsdrivesadaptiveresistancetomekerkinhibitorsthroughsrc
AT yangmingli ptprsdrivesadaptiveresistancetomekerkinhibitorsthroughsrc
AT wangheiman ptprsdrivesadaptiveresistancetomekerkinhibitorsthroughsrc
AT leechanggong ptprsdrivesadaptiveresistancetomekerkinhibitorsthroughsrc
AT yeatmantimothyj ptprsdrivesadaptiveresistancetomekerkinhibitorsthroughsrc
AT pledgerwjack ptprsdrivesadaptiveresistancetomekerkinhibitorsthroughsrc

Ejemplares similares