Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.omto.2021.10.005
Title: Cholesterol-enriched membrane micro-domain deficiency induces doxorubicin resistance via promoting autophagy in breast cancer
Authors: Shi, Yin 
Ye, Zu
Lu, Guang 
Yang, Naidi 
Zhang, Jianbin 
Wang, Liming 
Cui, Jianzhou 
del Pozo, Miguel A
Wu, Yihua
Xia, Dajing
Shen, Han-Ming
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
Medicine, Research & Experimental
Research & Experimental Medicine
CAVEOLAE-MEDIATED ENDOCYTOSIS
LIPID RAFTS
SNARE PROTEINS
RECYCLING ENDOSOME
AMYLOID-BETA
SYNTAXIN 6
FUSION
CELLS
TRAFFICKING
RICH
Issue Date: 1-Nov-2021
Publisher: CELL PRESS
Citation: Shi, Yin, Ye, Zu, Lu, Guang, Yang, Naidi, Zhang, Jianbin, Wang, Liming, Cui, Jianzhou, del Pozo, Miguel A, Wu, Yihua, Xia, Dajing, Shen, Han-Ming (2021-11-01). Cholesterol-enriched membrane micro-domain deficiency induces doxorubicin resistance via promoting autophagy in breast cancer. MOLECULAR THERAPY-ONCOLYTICS 23 : 311-329. ScholarBank@NUS Repository. https://doi.org/10.1016/j.omto.2021.10.005
Abstract: Drug resistance has become one of the largest challenges for cancer chemotherapies. Under certain conditions, cancer cells hijack autophagy to cope with therapeutic stress, which largely undermines the chemo-therapeutic efficacy. Currently, biomarkers indicative of autophagy-derived drug resistance remain largely inclusive. Here, we report a novel role of lipid rafts/cholesterol-enriched membrane micro-domains (CEMMs) in autophagosome biogenesis and doxorubicin resistance in breast tumors. We showed that CEMMs are required for the interaction of VAMP3 with syntaxin 6 (STX6, a cholesterol-binding SNARE protein). Upon disruption of CEMM, VAMP3 is released from STX6, resulting in the trafficking of ATG16L1-containing vesicles to recycling endosomes and subsequent autophagosome biogenesis. Furthermore, we found that CEMM marker CAV1 is decreased in breast cancer patients and that the CEMM deficiency-induced autophagy is related to doxorubicin resistance, which is overcome by autophagy inhibition. Taken together, we propose a novel model whereby CEMMs in recycling endosomes support the VAMP3 and STX6 interaction and function as barriers to limit the activity of VAMP3 in autophagic vesicle fusion, thus CEMM deficiency promotes autophagosome biogenesis and doxorubicin resistance in breast tumors.
Source Title: MOLECULAR THERAPY-ONCOLYTICS
URI: https://scholarbank.nus.edu.sg/handle/10635/224157
ISSN: 23727705
DOI: 10.1016/j.omto.2021.10.005
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
Cholesterol-enriched membrane micro-domaindeficiency induces doxorubicin resistancevia promoting autophagy in breast cancer.pdfPublished version6.46 MBAdobe PDF

OPEN

Post-printView/Download

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.