Identification of the MRTFA/SRF pathway as a critical regulator of quiescence in cancer.

Autor:	Panesso-Gómez S; Department of Internal Medicine and Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA, USA., Cole AJ; Department of Internal Medicine and Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA, USA., Wield A; Department of Internal Medicine and Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA, USA., Anyaeche VI; Department of Internal Medicine and Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA, USA., Shah J; Australian Centre for Blood Diseases, Central Clinical School, Monash University and Alfred Health, Melbourne, VIC, Australia., Jiang Q; Department of Internal Medicine and Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA, USA., Ebai T; Department of Internal Medicine and Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA, USA., Sharrow AC; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA., Tseng G; Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA., Yoon E; Department of Electrical Engineering, University of Michigan, Ann Arbor, MI, USA., Brown DD; Women's Cancer Research Center, Magee-Women's Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania., Clark AM; Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA., Larsen SD; Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan, USA., Eder I; Department of Bioengineering, University of Pittsburgh, PA, USA., Gau D; Department of Bioengineering, University of Pittsburgh, PA, USA., Roy P; Department of Bioengineering, University of Pittsburgh, PA, USA., Dahl KN; Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA., Tran L; Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA., Jiang H; Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA., McAuliffe PF; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA., Lee AV; Women's Cancer Research Center, Magee-Women's Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania., Buckanovich RJ; Department of Internal Medicine and Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA, USA.; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Nov 17. Date of Electronic Publication: 2024 Nov 17.
DOI:	10.1101/2024.11.15.623825
Abstrakt:	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.
Databáze:	MEDLINE
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