|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
5
|
|
pubmed:dateCreated |
2011-3-7
|
|
pubmed:abstractText |
Among breast cancers, triple-negative breast cancer (TNBC) is the most poorly understood and is refractory to current targeted therapies. Using a genetic screen, we identify the PTPN12 tyrosine phosphatase as a tumor suppressor in TNBC. PTPN12 potently suppresses mammary epithelial cell proliferation and transformation. PTPN12 is frequently compromised in human TNBCs, and we identify an upstream tumor-suppressor network that posttranscriptionally controls PTPN12. PTPN12 suppresses transformation by interacting with and inhibiting multiple oncogenic tyrosine kinases, including HER2 and EGFR. The tumorigenic and metastatic potential of PTPN12-deficient TNBC cells is severely impaired upon restoration of PTPN12 function or combined inhibition of PTPN12-regulated tyrosine kinases, suggesting that TNBCs are dependent on the proto-oncogenic tyrosine kinases constrained by PTPN12. Collectively, these data identify PTPN12 as a commonly inactivated tumor suppressor and provide a rationale for combinatorially targeting proto-oncogenic tyrosine kinases in TNBC and other cancers based on their profile of tyrosine-phosphatase activity.
|
|
pubmed:grant |
|
|
pubmed:commentsCorrections |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/EGFR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/MIRN124 microRNA, human,
http://linkedlifedata.com/resource/pubmed/chemical/MicroRNAs,
http://linkedlifedata.com/resource/pubmed/chemical/PTPN12 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Mar
|
|
pubmed:issn |
1097-4172
|
|
pubmed:author |
pubmed-author:AcetoNicolaN,
pubmed-author:Bentires-AljMohamedM,
pubmed-author:BernardiRonald JRJ,
pubmed-author:BoteroMariaM,
pubmed-author:CreightonChad JCJ,
pubmed-author:DephoureNoahN,
pubmed-author:ElledgeStephen JSJ,
pubmed-author:GibbsRichard ARA,
pubmed-author:GygiSteven PSP,
pubmed-author:HilsenbeckSusan GSG,
pubmed-author:HuGuangG,
pubmed-author:HuangJianJ,
pubmed-author:KesslerJessica DJD,
pubmed-author:LiMamie ZMZ,
pubmed-author:MeerbreyKristen LKL,
pubmed-author:MigliaccioIleniaI,
pubmed-author:MuznyDonnaD,
pubmed-author:NguyenDon XDX,
pubmed-author:OsborneC KentCK,
pubmed-author:PavlovaNatalya NNN,
pubmed-author:RaoMitchellM,
pubmed-author:SchiffRachelR,
pubmed-author:SchmittEarleneE,
pubmed-author:ShawChad ACA,
pubmed-author:SunTingtingT,
pubmed-author:WestbrookThomas FTF,
pubmed-author:WheelerDavid ADA,
pubmed-author:ZhouChunshuiC
|
|
pubmed:copyrightInfo |
Copyright © 2011 Elsevier Inc. All rights reserved.
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
4
|
|
pubmed:volume |
144
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
703-18
|
|
pubmed:meshHeading |
pubmed-meshheading:21376233-Breast Neoplasms,
pubmed-meshheading:21376233-Cell Line, Tumor,
pubmed-meshheading:21376233-Cell Transformation, Neoplastic,
pubmed-meshheading:21376233-Female,
pubmed-meshheading:21376233-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:21376233-Humans,
pubmed-meshheading:21376233-MAP Kinase Signaling System,
pubmed-meshheading:21376233-MicroRNAs,
pubmed-meshheading:21376233-Mutation,
pubmed-meshheading:21376233-Neoplasm Metastasis,
pubmed-meshheading:21376233-Protein Processing, Post-Translational,
pubmed-meshheading:21376233-Protein Tyrosine Phosphatase, Non-Receptor Type 12,
pubmed-meshheading:21376233-Receptor, Epidermal Growth Factor,
pubmed-meshheading:21376233-Tumor Suppressor Proteins
|
|
pubmed:year |
2011
|
|
pubmed:articleTitle |
Activation of multiple proto-oncogenic tyrosine kinases in breast cancer via loss of the PTPN12 phosphatase.
|
|
pubmed:affiliation |
Verna & Marrs McLean Department of Biochemistry & Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|
