Academic Journal
Src Inhibition Blocks c-Myc Translation and Glucose Metabolism to Prevent the Development of Breast Cancer
| العنوان: | Src Inhibition Blocks c-Myc Translation and Glucose Metabolism to Prevent the Development of Breast Cancer |
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| المؤلفون: | Jain, Shalini, Wang, Xiao, Chang, Chia-Chi, Ibarra-Drendall, Catherine, Wang, Hai, Zhang, Qingling, Brady, Samuel W., Li, Ping, Zhao, Hong, Dobbs, Jessica, Kyrish, Matt, Tkaczyk, Tomasz S., Ambrose, Adrian, Sistrunk, Christopher, Arun, Banu K., Richards-Kortum, Rebecca, Jia, Wei, Seewaldt, Victoria L., Yu, Dihua |
| بيانات النشر: | AACR |
| سنة النشر: | 2015 |
| المجموعة: | Rice University: Digital Scholarship Archive |
| الوصف: | Preventing 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | Jain, Shalini, Wang, Xiao, Chang, Chia-Chi, et al. "Src Inhibition Blocks c-Myc Translation and Glucose Metabolism to Prevent the Development of Breast Cancer." Cancer Research, 75, no. 22 (2015) AACR: 4863-4875. http://dx.doi.org/10.1158/0008-5472.CAN-14-2345.; https://hdl.handle.net/1911/94244; http://dx.doi.org/10.1158/0008-5472.CAN-14-2345 |
| DOI: | 10.1158/0008-5472.CAN-14-2345 |
| الاتاحة: | https://hdl.handle.net/1911/94244 https://doi.org/10.1158/0008-5472.CAN-14-2345 |
| Rights: | This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by AACR. |
| رقم الانضمام: | edsbas.2951B09B |
| قاعدة البيانات: | BASE |
| DOI: | 10.1158/0008-5472.CAN-14-2345 |
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