期刊
CELL REPORTS
卷 12, 期 3, 页码 511-524出版社
CELL PRESS
DOI: 10.1016/j.celrep.2015.06.044
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资金
- NIH [P30 CA125123, P30 AI036211, S10 RR024574, P01 GM81627, U54CA149196, R01 CA124820, P50-CA58183, P50-CA186784]
- NSF [DBI-0735191]
- Susan G. Komen for the Cure Foundation [PDF0707860]
- NCI Breast SPORE program [P50-CA58223-09A1]
- Breast Cancer Research Foundation
- Nancy Owens Memorial Foundation
- Mary Kay Ash Foundation
- Cancer Prevention and Research Institute of Texas (CPRIT) [RP130135]
Basal-like breast cancers (BLBCs) are aggressive, and their drivers are unclear. We have found that wild-type N-RAS is overexpressed in BLBCs but not in other breast cancer subtypes. Repressing N-RAS inhibits transformation and tumor growth, whereas overexpression enhances these processes even in preinvasive BLBC cells. We identified N-Ras-responsive genes, most of which encode chemokines; e.g., IL8. Expression levels of these chemokines and N-RAS in tumors correlate with outcome. N-Ras, but not K-Ras, induces IL-8 by binding and activating the cytoplasmic pool of JAK2; IL-8 then acts on both the cancer cells and stromal fibroblasts. Thus, BLBC progression is promoted by increasing activities of wild-type N-Ras, which mediates autocrine/paracrine signaling that can influence both cancer and stroma cells.
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