Journal
BREAST CANCER
Volume 28, Issue 2, Pages 355-367Publisher
SPRINGER JAPAN KK
DOI: 10.1007/s12282-020-01166-0
Keywords
EZH2; Tamoxifen; Breast cancer
Categories
Funding
- DBT
- DST
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This study elucidated the global change in proteome profile of tamoxifen-resistant MCF-7 breast cancer cells upon EZH2 knockdown, revealing proteins previously unrecognized for their role in tamoxifen resistance and their association with breast cancer patient survival. Targeting EZH2 or downstream molecules may be helpful in reacquiring sensitivity to tamoxifen in breast cancer.
Background Acquired 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. Methods Tamoxifen 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. Results Here, 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. Conclusion Overall, 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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