Back to Search Start Over

TRAF6 promotes chemoresistance to paclitaxel of triple negative breast cancer via regulating PKM2‐mediated glycolysis

Authors :
Han Xu
Longzhi Li
Bing Dong
Ji Lu
Kun Zhou
Xiaoxing Yin
Huizhen Sun
Source :
Cancer Medicine, Vol 12, Iss 19, Pp 19807-19820 (2023)
Publication Year :
2023
Publisher :
Wiley, 2023.

Abstract

Abstract Ample evidence reveals that glycolysis is crucial to tumor progression; however, the underlying mechanism of its drug resistance is still worth being further explored. TRAF6, an E3 ubiquitin ligase, is well recognized to overexpress in various types of cancer, which predicts a poor prognosis. In our study, we discovered that TRAF6 was expressed more significantly in the case of triple‐negative breast cancer (TNBC) than in other of breast cancers, promoting chemoresistance to paclitaxel; that inhibited TRAF6 expression in the chemoresistant TNBC (TNBC‐CR) cells enhanced the sensitivity by decreasing glucose uptake and lactate production; that TRAF6 regulated glycolysis and facilitated chemoresistance via binding directly to PKM2; and that overexpressing PKM2 in the TNBC‐CR cells with TRAF6 knocked down regained significantly TRAF6‐dependent drug resistance and glycolysis. Additionally, we verified that TRAF6 could facilitate PKM2‐mediated glycolysis and chemoresistance in animal models and clinical tumor tissues. Thus, we identified the novel function of TRAF6 to promote glycolysis and drug resistance in TNBC with the regulation of PKM2, which could provide a potential molecular target for TNBC treatment.

Details

Language :
English
ISSN :
20457634
Volume :
12
Issue :
19
Database :
Directory of Open Access Journals
Journal :
Cancer Medicine
Publication Type :
Academic Journal
Accession number :
edsdoj.8cc7f3b9dcd94b9c8813d69d349f5494
Document Type :
article
Full Text :
https://doi.org/10.1002/cam4.6552