ArticleCell death & disease2012
Paclitaxel resistance is associated with switch from apoptotic to autophagic cell death in MCF-7 breast cancer cells.
Article in Cell death & disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 184 citations in OpenAlex.
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- Prognostic, diagnostic and therapeutic value of the cancer tubulin code.Cancer metastasis reviews · 2026Review
- Omega-3 fatty acids: molecular weapons against chemoresistance in breast cancer.Cellular & molecular biology letters · 2025Review
- Role of EMT in drug resistance of breast cancer: molecular mechanisms and therapeutic strategies.Frontiers in oncology · 2025Review
- PFDN4 as a Prognostic Marker Was Associated with Chemotherapy Resistance through CREBP1/AURKA Pathway in Triple-Negative Breast Cancer.International journal of molecular sciences · 2024Article
- EEBR induces Caspase-1-dependent pyroptosis through the NF-κB/NLRP3 signalling cascade in non-small cell lung cancer.Journal of cellular and molecular medicine · 2024Article
- The Role of Intracellular and Extracellular Vesicles in the Development of Therapy Resistance in Cancer.Current pharmaceutical design · 2024Review
- Different types of cell death and their shift in shaping disease.Cell death discovery · 2023Review
- BMP signaling inhibition overcomes chemoresistance of prostate cancer.American journal of cancer research · 2023Article
- Mechanisms of cancer cell death induction by paclitaxel: an updated review.Apoptosis : an international journal on programmed cell death · 2022Review
- Hormonal and Genetic Regulatory Events in Breast Cancer and Its Therapeutics: Importance of the Steroidogenic Acute Regulatory Protein.Biomedicines · 2022Review
- Water Dynamics in Cancer Cells: Lessons from Quasielastic Neutron Scattering.Medicina (Kaunas, Lithuania) · 2022Review
- Article
- Ubiquitination of NF-κB p65 by FBXW2 suppresses breast cancer stemness, tumorigenesis, and paclitaxel resistance.Cell death and differentiation · 2022Article
- Modulation of Autophagy in Adrenal Tumors.Frontiers in endocrinology · 2022Review
- Targeted Pyroptosis Is a Potential Therapeutic Strategy for Cancer.Journal of oncology · 2022Review
- The MicroRNA-Based Strategies to Combat Cancer ChemoresistanceFrontiers in oncology · 2022Review
- Review
- Development and Validation of a 5-Gene Autophagy-Based Prognostic Index in Endometrial Carcinoma.Medical science monitor : international medical journal of experimental and clinical research · 2021Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Taxanes remain first line chemotherapy in management of metastatic breast cancer and have a key role in epithelial ovarian cancer, with increasingly common use of weekly paclitaxel dosing regimens. However, their clinical utility is limited by the development of chemoresistance. To address this, we modelled in vitro paclitaxel resistance in MCF-7 cells. We show that at clinically relevant drug doses, emerging paclitaxel resistance is associated with profound changes in cell death responses and a switch from apoptosis to autophagy as the principal mechanism of drug-induced cytotoxicity. This was characterised by a complete absence of caspase-mediated apoptotic cell death (using the pan-caspase-inhibitor Z-VAD) in paclitaxel-resistant MCF-7TaxR cells, compared with parent MCF-7 or MDA-MB-231 cell lines on paclitaxel challenge, downregulation of caspase-7, caspase-9 and BCl2-interacting mediator of cell death (BIM) expression. Silencing with small interfering RNA to BIM in MCF-7 parental cells was sufficient to confer paclitaxel resistance, inferring the significance in downregulation of this protein in contributing to the resistant phenotype of the MCF-7TaxR cell line. Conversely, there was an increased autophagic response in the MCF-7TaxR cell line with reduced phospho-mTOR and relative resistance to the mTOR inhibitors rapamycin and RAD001. In conclusion, we show for the first time that paclitaxel resistance is associated with profound changes in cell death response with deletion of multiple apoptotic factors balanced by upregulation of the autophagic pathway and collateral sensitivity to platinum.
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