| Literature DB >> 25759021 |
Young Joo Jeon1, Sihem Khelifa2, Boris Ratnikov1, David A Scott1, Yongmei Feng1, Fabio Parisi2, Chelsea Ruller1, Eric Lau1, Hyungsoo Kim1, Laurence M Brill1, Tingting Jiang2, David L Rimm2, Robert D Cardiff3, Gordon B Mills4, Jeffrey W Smith1, Andrei L Osterman1, Yuval Kluger2, Ze'ev A Ronai5.
Abstract
Many tumor cells are fueled by altered metabolism and increased glutamine (Gln) dependence. We identify regulation of the L-glutamine carrier proteins SLC1A5 and SLC38A2 (SLC1A5/38A2) by the ubiquitin ligase RNF5. Paclitaxel-induced ER stress to breast cancer (BCa) cells promotes RNF5 association, ubiquitination, and degradation of SLC1A5/38A2. This decreases Gln uptake, levels of TCA cycle components, mTOR signaling, and proliferation while increasing autophagy and cell death. Rnf5-deficient MMTV-PyMT mammary tumors were less differentiated and showed elevated SLC1A5 expression. Whereas RNF5 depletion in MDA-MB-231 cells promoted tumorigenesis and abolished paclitaxel responsiveness, SLC1A5/38A2 knockdown elicited opposing effects. Inverse RNF5(hi)/SLC1A5/38A2(lo) expression was associated with positive prognosis in BCa. Thus, RNF5 control of Gln uptake underlies BCa response to chemotherapies.Entities:
Mesh：
Substances：
Year: 2015 PMID： 25759021 PMCID： PMC4356903 DOI： 10.1016/j.ccell.2015.02.006
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743