Wild-Type N-Ras, Overexpressed in Basal-like Breast Cancer, Promotes Tumor Formation by Inducing IL-8 Secretion via JAK2 Activation
Year: 2015
Type: article
Abstract: 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.
Source: Cell Reports
Authors: Ze-Yi Zheng, Lin Tian, Wen Bu, Cheng Fan, Xia Gao, Hai Wang, Yi-Hua Liao, Yi Li, Michael T. Lewis, Dean Edwards, Thomas P. Zwaka, Susan G. Hilsenbeck, Daniel Medina, Charles M. Perou, Chad J. Creighton, Xiang H.-F. Zhang, Eric C. Chang
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: National Science Foundation, Cancer Prevention and Research Institute of Texas, Nancy Owens Memorial Foundation, National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, Division of Materials Research, National Center for Research Resources
Awards: G108258030, G1569999668, G202784131, BD Biosciences Special Order LSRII, G2663554855, Regulatory Networks in Human Embryonic Stem Cells, G277360231, Translational Research in Breast Cancer, G418187648, G500662192, G5248451359, Center for Systematic Modeling of Cancer Development, PSCIC Full Proposal: The iPlant Collaborative: A Cyberinfrastructure-Centered Community for a New Plant Biology, Translational Research in Breast Cancer, Selective control of multiple Ras signaling activities, G746461529, G7837447426, G8153776008, G863484009, G9000018430, G9000063720, G9000065690, G9000198215, G9000240210, Baylor College of Medicine Cancer Center - Cancer Center Support Grant, G949115552, G99424851
OpenAlex ID: W1505153529