ArticleBreast cancer (Tokyo, Japan)2021
EZH2 knockdown in tamoxifen-resistant MCF-7 cells unravels novel targets for regaining sensitivity towards tamoxifen.
Article in Breast cancer (Tokyo, Japan), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed, 6 citations in OpenAlex.
- Targeting ZNF570 activates ferroptosis to reverse tamoxifen resistance in ER + breast cancer cells.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- HNRNPA2B1 regulates tamoxifen- and fulvestrant-sensitivity and hallmarks of endocrine resistance in breast cancer cells.Cancer letters · 2021Article
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4 authors at 3 institutions in 1 country.
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Abstract
backgroundAcquired resistance to drug involves multilayered genetic and epigenetic regulation. Inhibition of EZH2 has proven to reverse the tamoxifen resistance back to the sensitive state in breast cancer. However, the molecular players involved in EZH2-mediated effects on tamoxifen-resistant MCF-7 cells are unknown. This study was conducted to understand the global change in proteome profile of tamoxifen-resistant MCF-7 breast cancer cells upon EZH2 knockdown.
methodsTamoxifen resistance MCF-7 breast cancer cells were established using increasing concentrations of 4-hydroxy tamoxifen. Using label free proteomics approach, we studied the alteration in total proteome in resistant cells as well as cells transfected with siEZH2 in comparison to sensitive and cells transfected with non-targeting siRNA.
resultsHere, we report list of proteins that were previously not recognized for their role in tamoxifen resistance and hold a close association with breast cancer patient survival. Proteins Annexin A2, CD44, nucleosome assembly protein 1, and lamin A/C were among the most upregulated protein in tamoxifen-resistant cells that were found to be abrogated upon EZH2 knockdown. The study suggests the involvement for various proteins in acquiring resistance towards tamoxifen and anticipates further research for investigating their therapeutic potentials.
conclusionOverall, we propose that targeting EZH2 or the molecules down the cascade might be helpful in reacquiring sensitivity to tamoxifen in breast cancer.
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