1. Identification of the MRTFA/SRF pathway as a critical regulator of quiescence in cancer.
- Author
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Panesso-Gómez S, Cole AJ, Wield A, Anyaeche VI, Shah J, Jiang Q, Ebai T, Sharrow AC, Tseng G, Yoon E, Brown DD, Clark AM, Larsen SD, Eder I, Gau D, Roy P, Dahl KN, Tran L, Jiang H, McAuliffe PF, Lee AV, and Buckanovich RJ
- Abstract
Chemoresistance is a major driver of cancer deaths. One understudied mechanism of chemoresistance is quiescence. We used single cell culture to identify, retrieve, and RNA-Seq profile primary quiescent ovarian cancer cells (qOvCa). We found that many qOvCa differentially expressed genes are transcriptional targets of the Myocardin Related Transcription Factor/Serum Response Factor (MRTF/SRF) pathway. We also found that genetic disruption of MRTF-SRF interaction, or an MRTF/SRF inhibitor (CCG257081) impact qOvCa gene expression and induce a quiescent state in cancer cells. Suggesting a broad role for this pathway in quiescence, CCG257081 treatment induced quiescence in breast, lung, colon, pancreatic and ovarian cancer cells. Furthermore, CCG081 (i) maintained a quiescent state in patient derived breast cancer organoids and, (ii) induced tumor growth arrest in ovarian cancer xenografts. Together, these data suggest that MRTF/SRF pathway is a critical regulator of quiescence in cancer and a possible therapeutic target., Competing Interests: The authors have declared that no conflict of interest exists. Competing interests The authors declare no competing interests.
- Published
- 2024
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