dc.contributor.author | Muranen, Taru | |
dc.contributor.author | Selfors, Laura M. | |
dc.contributor.author | Hwang, Julie | |
dc.contributor.author | Gallegos, Lisa L. | |
dc.contributor.author | Coloff, Jonathan L. | |
dc.contributor.author | Mills, Gordon B. | |
dc.contributor.author | Brugge, Joan S. | |
dc.contributor.author | Thoreen, Carson C | |
dc.contributor.author | Kang, Seong-Cheol | |
dc.contributor.author | Sabatini, David | |
dc.date.accessioned | 2018-07-05T13:44:25Z | |
dc.date.available | 2018-07-05T13:44:25Z | |
dc.date.issued | 2016-10 | |
dc.date.submitted | 2016-09 | |
dc.identifier.issn | 0008-5472 | |
dc.identifier.issn | 1538-7445 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/116784 | |
dc.description.abstract | Aberrant activation of the PI3K/mTOR pathway is a common feature of many cancers and an attractive target for therapy, but resistance inevitably evolves as is the case for any cancer cell-targeted therapy. In animal tumor models, chronic inhibition of PI3K/mTOR initially inhibits tumor growth, but over time, tumor cells escape inhibition. In this study, we identified a context-dependent mechanism of escape whereby tumor cells upregulated the proto-oncogene transcriptional regulators c-MYC and YAP1. This mechanism was dependent on both constitutive ERK activity as well as inhibition of the stress kinase p38. Inhibition of p38 relieved proliferation arrest and allowed upregulation of MYC and YAP through stabilization of CREB. These data provide new insights into cellular signaling mechanisms that influence resistance to PI3K/mTOR inhibitors. Furthermore, they suggest that therapies that inactivate YAP or MYC or augment p38 activity could enhance the efficacy of PI3K/mTOR inhibitors. | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (Grant R01CA103866) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (Grant AI47389) | en_US |
dc.publisher | American Association for Cancer Research (AACR) | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1158/0008-5472.CAN-16-0155 | en_US |
dc.rights | Creative Commons Attribution-Noncommercial-Share Alike | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | en_US |
dc.source | PMC | en_US |
dc.title | ERK and p38 MAPK Activities Determine Sensitivity to PI3K/mTOR Inhibition via Regulation of MYC and YAP | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Muranen, Taru et al. “ERK and P38 MAPK Activities Determine Sensitivity to PI3K/mTOR Inhibition via Regulation of MYC and YAP.” Cancer Research 76, 24 (October 2016): 7168–7180 © 2016 American Association for Cancer Research (AACR) | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.department | Koch Institute for Integrative Cancer Research at MIT | en_US |
dc.contributor.mitauthor | Thoreen, Carson C | |
dc.contributor.mitauthor | Kang, Seong-Cheol | |
dc.contributor.mitauthor | Sabatini, David | |
dc.relation.journal | Cancer Research | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dc.date.updated | 2018-07-03T18:28:32Z | |
dspace.orderedauthors | Muranen, Taru; Selfors, Laura M.; Hwang, Julie; Gallegos, Lisa L.; Coloff, Jonathan L.; Thoreen, Carson C.; Kang, Seong A.; Sabatini, David M.; Mills, Gordon B.; Brugge, Joan S. | en_US |
dspace.embargo.terms | N | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-1446-7256 | |
mit.license | OPEN_ACCESS_POLICY | en_US |