التفاصيل البيبلوغرافية
| العنوان: |
Loss of RasGAP tumor suppressors underlie the aggressive nature of luminal B breast cancers |
| المؤلفون: |
Yoko S. DeRose, Sandra S. McAllister, Wenhui Zhou, Ann H. Partridge, Ania Wronski, Sarah Naomi Olsen, Karen Cichowski, Charlotte Kuperwasser, Clare F. Malone, Alana L. Welm, Thomas De Raedt, Stephanie Guerra, Zafira Castaño, Massimo Loda, Miriam Enos, Benjamin Dake |
| سنة النشر: |
2016 |
| مصطلحات موضوعية: |
0301 basic medicine, Epithelial-Mesenchymal Transition, GTPase-activating protein, Estrogen receptor, Breast Neoplasms, Biology, Article, law.invention, Metastasis, Pathogenesis, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, Mice, law, Cell Line, Tumor, medicine, Animals, Humans, Epithelial–mesenchymal transition, Neoplasm Metastasis, GTPase-Activating Proteins, NF-kappa B, Cancer, medicine.disease, 030104 developmental biology, Oncology, ras GTPase-Activating Proteins, Immunology, Mutation, Cancer research, Disease Progression, MCF-7 Cells, Suppressor, Female, Signal transduction, Carrier Proteins, Neoplasm Transplantation, Signal Transduction |
| الوصف: |
Luminal breast cancers are typically estrogen receptor–positive and generally have the best prognosis. However, a subset of luminal tumors, namely luminal B cancers, frequently metastasize and recur. Unfortunately, the causal events that drive their progression are unknown, and therefore it is difficult to identify individuals who are likely to relapse and should receive escalated treatment. Here, we identify a bifunctional RasGAP tumor suppressor whose expression is lost in almost 50% of luminal B tumors. Moreover, we show that two RasGAP genes are concomitantly suppressed in the most aggressive luminal malignancies. Importantly, these genes cooperatively regulate two major oncogenic pathways, RAS and NF-κB, through distinct domains, and when inactivated drive the metastasis of luminal tumors in vivo. Finally, although the cooperative effects on RAS drive invasion, NF-κB activation triggers epithelial-to-mesenchymal transition and is required for metastasis. Collectively, these studies reveal important mechanistic insight into the pathogenesis of luminal B tumors and provide functionally relevant prognostic biomarkers that may guide treatment decisions. Significance: The lack of insight into mechanisms that underlie the aggressive behavior of luminal B breast cancers impairs treatment decisions and therapeutic advances. Here, we show that two RasGAP tumor suppressors are concomitantly suppressed in aggressive luminal B tumors and demonstrate that they drive metastasis by activating RAS and NF-κB. Cancer Discov; 7(2); 202–17. ©2016 AACR. See related commentary by Sears and Gray, p. 131. This article is highlighted in the In This Issue feature, p. 115 |
| اللغة: |
English |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0b32cbedc33a4e5a2916062711586f50
https://europepmc.org/articles/PMC6461361/ |
| حقوق: |
OPEN |
| رقم الأكسشن: |
edsair.doi.dedup.....0b32cbedc33a4e5a2916062711586f50 |
| قاعدة البيانات: |
OpenAIRE |
