Knockdown of YAP/TAZ sensitizes tamoxifen-resistant MCF7 breast cancer cells

• Published in: Biochemical and biophysical research communications Vol. 601; pp. 73 - 78
• Main Authors: Kim, Yu Jin, Jang, Se-Kyeong, Hong, Sung-Eun, Park, Chan Sub, Seong, Min-Ki, Kim, Hyun-Ah, Park, Ki Soo, Kim, Chun-Ho, Park, In-Chul, Jin, Hyeon-Ok
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23.04.2022
• Subjects: Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Cell Line, Tumor; Drug Resistance, Neoplasm; Estrogen receptor; Female; Humans; MCF-7 Cells; Mechanistic Target of Rapamycin Complex 1; PSAT1; RNA, Small Interfering; Survivin - genetics; Tamoxifen - pharmacology; Tamoxifen resistance; Transcriptional Coactivator with PDZ-Binding Motif Proteins - metabolism; YAP-Signaling Proteins - metabolism; YAP/TAZ; Estrogen receptor; Breast cancer; PSAT1; Tamoxifen resistance; YAP/TAZ
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2022.02.083

Although endocrine therapy with tamoxifen has improved survival in breast cancer patients, resistance to this therapy remains one of the major causes of breast cancer mortality. In the present study, we found that the expression level of YAP/TAZ in tamoxifen-resistant MCF7 (MCF7-TR) breast cancer cells was significantly increased compared with that in MCF7 cells. Knockdown of YAP/TAZ with siRNA sensitized MCF7-TR cells to tamoxifen. Furthermore, siRNA targeting PSAT1, a downstream effector of YAP/TAZ, enhanced sensitivity to tamoxifen in MCF7-TR cells. Additionally, mTORC1 activity and survivin expression were significantly decreased during cell death induced by combination treatment with YAP/TAZ or PSAT1 siRNA and tamoxifen. In conclusion, targeting the YAP/TAZ-PSAT1 axis could sensitize tamoxifen-resistant MCF7 breast cancer cells by modulating the mTORC1-survivin axis. •YAP/TAZ expression is elevated in tamoxifen (TAM)-resistant breast cancer cells.•YAP/TAZ upregulates PSAT1 expression in TAM-resistant breast cancer cells.•YAP/TAZ or PSAT1 knockdown overcomes TAM resistance by modulating mTORC1/survivin.