Anoikis resistance and metastasis of ovarian cancer can be overcome by CDK8/19 Mediator kinase inhibition.
Date
2026-01-15
Journal Title
Journal ISSN
Volume Title
Publisher
JCI Insight
Abstract
Anoikis resistance or evasion of cell death triggered by matrix detachment is a hallmark of cancer cell survival and metastasis. We show that repeated exposure to suspension stress followed by recovery under attached conditions leads to development of anoikis resistance. The acquisition of anoikis resistance is associated with enhanced invasion, chemoresistance, and immune evasion in vitro and distant metastasis in vivo. This acquired anoikis resistance is not genetic, persisting for a finite duration without detachment stress, but is sensitive to CDK8/19 Mediator kinase inhibition that can also reverse anoikis resistance. Transcriptomic analysis reveals that CDK8/19 kinase inhibition induces bidirectional transcriptional changes in both sensitive and resistant cells, disrupting the balanced reprogramming required for anoikis adaptation and resistance by reversing some resistance associated pathways and enhancing others. Both anoikis resistance and in vivo metastatic growth of ovarian cancers are sensitive to CDK8/19 inhibition, thereby providing a therapeutic opportunity to both prevent and suppress ovarian cancer metastasis.
Description
This article was originally published in JCI Insight. The version of record is available at: https://doi.org/10.1172/jci.insight.192113
Copyright © 2026, Monavarian et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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Citation
Monavarian, M., Rajkarnikar, R., Page, E. F., Kumari, A., Quintero Macias, L., Massicano, F., Lee, N. Y., Sahoo, S., Hempel, N., Jolly, M. K., Ianov, L., Worthey, E., Singh, A., Roninson, I. B., Broude, E. V., Chen, M., & Mythreye, K. (2026). Anoikis resistance and metastasis of ovarian cancer can be overcome by CDK8/19 Mediator kinase inhibition. JCI Insight. https://doi.org/10.1172/jci.insight.192113