dc.contributor.author | Noll, Elisa M. | |
dc.contributor.author | Sprick, Martin R. | |
dc.contributor.author | Trumpp, Andreas | |
dc.contributor.author | Muzumdar, Mandar | |
dc.contributor.author | Chen, Pan-Yu | |
dc.contributor.author | Dorans, Kimberly | |
dc.contributor.author | Chung, Katherine Minjee | |
dc.contributor.author | Bhutkar, Arjun | |
dc.contributor.author | Hong, Erin | |
dc.contributor.author | Jacks, Tyler E. | |
dc.date.accessioned | 2017-12-11T19:48:01Z | |
dc.date.available | 2017-12-11T19:48:01Z | |
dc.date.issued | 2017-10 | |
dc.date.submitted | 2017-06 | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/112693 | |
dc.description.abstract | Activating mutations in the proto-oncogene KRAS are a hallmark of pancreatic ductal adenocarcinoma (PDAC), an aggressive malignancy with few effective therapeutic options. Despite efforts to develop KRAS-targeted drugs, the absolute dependence of PDAC cells on KRAS remains incompletely understood. Here we model complete KRAS inhibition using CRISPR/Cas-mediated genome editing and demonstrate that KRAS is dispensable in a subset of human and mouse PDAC cells. Remarkably, nearly all KRAS deficient cells exhibit phosphoinositide 3-kinase (PI3K)-dependent mitogen-activated protein kinase (MAPK) signaling and induced sensitivity to PI3K inhibitors. Furthermore, comparison of gene expression profiles of PDAC cells retaining or lacking KRAS reveal a role of KRAS in the suppression of metastasis-related genes. Collectively, these data underscore the potential for PDAC resistance to even the very best KRAS inhibitors and provide insights into mechanisms of response and resistance to KRAS inhibition. | en_US |
dc.publisher | Nature Publishing Group | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1038/s41467-017-00942-5 | en_US |
dc.rights | Creative Commons Attribution 4.0 International | en_US |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_US |
dc.source | Nature | en_US |
dc.title | Survival of pancreatic cancer cells lacking KRAS function | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Muzumdar, Mandar Deepak et al. “Survival of Pancreatic Cancer Cells Lacking KRAS Function.” Nature Communications 8, 1 (October 2017): 1090 © 2017 The Author(s) | 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 | Muzumdar, Mandar | |
dc.contributor.mitauthor | Chen, Pan-Yu | |
dc.contributor.mitauthor | Dorans, Kimberly | |
dc.contributor.mitauthor | Chung, Katherine Minjee | |
dc.contributor.mitauthor | Bhutkar, Arjun | |
dc.contributor.mitauthor | Hong, Erin | |
dc.contributor.mitauthor | Jacks, Tyler E. | |
dc.relation.journal | Nature Communications | en_US |
dc.eprint.version | Final published version | 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 | 2017-12-11T18:31:16Z | |
dspace.orderedauthors | Muzumdar, Mandar Deepak; Chen, Pan-Yu; Dorans, Kimberly Judith; Chung, Katherine Minjee; Bhutkar, Arjun; Hong, Erin; Noll, Elisa M.; Sprick, Martin R.; Trumpp, Andreas; Jacks, Tyler | en_US |
dspace.embargo.terms | N | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-4450-7570 | |
dc.identifier.orcid | https://orcid.org/0000-0001-9119-8718 | |
dc.identifier.orcid | https://orcid.org/0000-0001-5785-8911 | |
dspace.mitauthor.error | true | |
mit.license | PUBLISHER_CC | en_US |
mit.metadata.status | Complete | |