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dc.contributor.authorShrestha, Yashaswi
dc.contributor.authorSchafer, Eric J.
dc.contributor.authorBoehm, Jesse S.
dc.contributor.authorHe, Frank
dc.contributor.authorWang, Shumei
dc.contributor.authorBarretina, Jordi
dc.contributor.authorThomas, Sapana Rachael
dc.contributor.authorDu, Jinyan
dc.contributor.authorWeir, Barbara Ann
dc.contributor.authorZhao, Jean J.
dc.contributor.authorGolub, Todd R.
dc.contributor.authorBeroukhim, Rameen
dc.contributor.authorHahn, William C.
dc.contributor.authorPolyak, Kornelia
dc.date.accessioned2013-05-08T14:00:21Z
dc.date.issued2012
dc.identifier.citationShrestha, Yashaswi, Eric J. Schafer, Jesse S. Boehm, Sapana Rachael Thomas, Frank He, Jinyan Du, Shumei Wang, et al. 2012. PAK1 is a breast cancer oncogene that coordinately activates MAPK and MET signaling. Oncogene 31(29): 3397-3408.en_US
dc.identifier.issn0950-9232en_US
dc.identifier.issn1476-5594en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10612552
dc.description.abstractActivating mutations in the RAS family or BRAF frequently occur in many types of human cancers but are rarely detected in breast tumors. However, activation of the RAS-RAF-MEK-ERK Mitogen-Activated Protein Kinase (MAPK) pathway is commonly observed in human breast cancers, suggesting that other genetic alterations lead to activation of this signaling pathway. To identify breast cancer oncogenes that activate the MAPK pathway, we screened a library of human kinases for their ability to induce anchorage-independent growth in a derivative of immortalized human mammary epithelial cells (HMLE). We identified PAK1 as a kinase that permitted HMLE cells to form anchorage-independent colonies. PAK1 is amplified in several human cancer types, including 33% of breast tumor samples and cancer cell lines. The kinase activity of PAK1 is necessary for PAK1-induced transformation. Moreover, we show that PAK1 simultaneously activates MAPK and MET signaling; the latter via inhibition of Merlin. Disruption of these activities inhibits PAK1-driven anchorage-independent growth. These observations establish PAK1 amplification as an alternative mechanism for MAPK activation in human breast cancer and credential PAK1 as a breast cancer oncogene that coordinately regulates multiple signaling pathways, the cooperation of which leads to malignant transformation.en_US
dc.language.isoen_USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofdoi:10.1038/onc.2011.515en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291810/pdf/en_US
dash.licenseLAA
dc.subjectPAK1en_US
dc.subjecttransformationen_US
dc.subjectoncogeneen_US
dc.subjectMAPKen_US
dc.subjectMETen_US
dc.subjectMerlinen_US
dc.titlePAK1 is a Breast Cancer Oncogene that Coordinately Activates MAPK and MET Signalingen_US
dc.typeJournal Articleen_US
dc.description.versionAccepted Manuscripten_US
dc.relation.journalOncogeneen_US
dash.depositing.authorWeir, Barbara Ann
dc.date.available2013-05-08T14:00:21Z
dc.identifier.doi10.1038/onc.2011.515*
dash.authorsorderedfalse
dash.contributor.affiliatedThomas, Sapana Rachael
dash.contributor.affiliatedDu, Jinyan
dash.contributor.affiliatedZhao, Jean
dash.contributor.affiliatedWeir, Barbara Ann
dash.contributor.affiliatedGolub, Todd
dash.contributor.affiliatedPolyak, Kornelia
dash.contributor.affiliatedHahn, William
dash.contributor.affiliatedBeroukhim, Rameen


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