ArticleMolecular therapy oncolytics2021
Cholesterol-enriched membrane micro-domaindeficiency induces doxorubicin resistancevia promoting autophagy in breast cancer.
Article in Molecular therapy oncolytics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Article
- Cholesterol metabolism and cancer: Molecular mechanisms, immune regulation and an epidemiological perspective (Review).International journal of molecular medicine · 2025Review
- VAMP proteins: molecular architects in disease pathogenesis and therapeutic innovation.Medical oncology (Northwood, London, England) · 2025Review
- The role of fatty acid metabolism on B cells and B cell-related autoimmune diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Autophagy in doxorubicin resistance: basic concepts, therapeutic perspectives and clinical translation.Frontiers in immunology · 2025Review
- CCAAT enhancer binding protein delta activates vesicle associated membrane protein 3 transcription to enhance chemoresistance and extracellular PD-L1 expression in triple-negative breast cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- Cholesterol metabolism in tumor microenvironment: cancer hallmarks and therapeutic opportunities.International journal of biological sciences · 2024Review
- Reprogramming of Lipid Metabolism Mediates Crosstalk, Remodeling, and Intervention of Microenvironment Components in Breast Cancer.International journal of biological sciences · 2024Review
- Dysregulation of Fatty Acid Metabolism in Breast Cancer and Its Targeted Therapy.Breast cancer (Dove Medical Press) · 2024Review
- The Effect of Cholesterol in MCF7 Human Breast Cancer Cells.International journal of molecular sciences · 2023Article
- Syntaxin-6 promotes the progression of hepatocellular carcinoma and alters its sensitivity to chemotherapies by activating the USF2/LC3B axis.International journal of biological sciences · 2023Article
- SDC1-TGM2-FLOT1-BHMT complex determines radiosensitivity of glioblastoma by influencing the fusion of autophagosomes with lysosomes.Theranostics · 2023Article
- Role of STX6 as a prognostic factor associated with immune infiltration in hepatocellular carcinoma.Oncology letters · 2022Article
- Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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