Src Inhibition Blocks c-Myc Translation and Glucose Metabolism to Prevent the Development of Breast Cancer

Simple item page
dc.citation.firstpage4863
dc.citation.issueNumber22
dc.citation.journalTitleCancer Research
dc.citation.lastpage4875
dc.citation.volumeNumber75
dc.contributor.authorJain, Shalini
dc.contributor.authorWang, Xiao
dc.contributor.authorChang, Chia-Chi
dc.contributor.authorIbarra-Drendall, Catherine
dc.contributor.authorWang, Hai
dc.contributor.authorZhang, Qingling
dc.contributor.authorBrady, Samuel W.
dc.contributor.authorLi, Ping
dc.contributor.authorZhao, Hong
dc.contributor.authorDobbs, Jessica
dc.contributor.authorKyrish, Matt
dc.contributor.authorTkaczyk, Tomasz S.
dc.contributor.authorAmbrose, Adrian
dc.contributor.authorSistrunk, Christopher
dc.contributor.authorArun, Banu K.
dc.contributor.authorRichards-Kortum, Rebecca
dc.contributor.authorJia, Wei
dc.contributor.authorSeewaldt, Victoria L.
dc.contributor.authorYu, Dihua
dc.date.accessioned2017-05-12T17:10:13Z
dc.date.available2017-05-12T17:10:13Z
dc.date.issued2015
dc.description.abstractPreventing breast cancer will require the development of targeted strategies that can effectively block disease progression. Tamoxifen and aromatase inhibitors are effective in addressing estrogen receptor–positive (ER+) breast cancer development, but estrogen receptor–negative (ER−) breast cancer remains an unmet challenge due to gaps in pathobiologic understanding. In this study, we used reverse-phase protein array to identify activation of Src kinase as an early signaling alteration in premalignant breast lesions of women who did not respond to tamoxifen, a widely used ER antagonist for hormonal therapy of breast cancer. Src kinase blockade with the small-molecule inhibitor saracatinib prevented the disorganized three-dimensional growth of ER− mammary epithelial cells in vitro and delayed the development of premalignant lesions and tumors in vivo in mouse models developing HER2+ and ER− mammary tumors, extending tumor-free and overall survival. Mechanistic investigations revealed that Src blockade reduced glucose metabolism as a result of an inhibition in ERK1/2–MNK1–eIF4E–mediated cap-dependent translation of c-Myc and transcription of the glucose transporter GLUT1, thereby limiting energy available for cell growth. Taken together, our results provide a sound rationale to target Src pathways in premalignant breast lesions to limit the development of breast cancers.
dc.identifier.citationJain, Shalini, Wang, Xiao, Chang, Chia-Chi, et al.. "Src Inhibition Blocks c-Myc Translation and Glucose Metabolism to Prevent the Development of Breast Cancer." <i>Cancer Research,</i> 75, no. 22 (2015) AACR: 4863-4875. http://dx.doi.org/10.1158/0008-5472.CAN-14-2345.
dc.identifier.doihttp://dx.doi.org/10.1158/0008-5472.CAN-14-2345
dc.identifier.urihttps://hdl.handle.net/1911/94244
dc.language.isoeng
dc.publisherAACR
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by AACR.
dc.titleSrc Inhibition Blocks c-Myc Translation and Glucose Metabolism to Prevent the Development of Breast Cancer
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpost-print
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Src-Inhibition.pdf
Size:
1.18 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Faculty Publications
Bioengineering Publications