Unknown

Dataset Information

0

Development of adaptive anoikis resistance promotes metastasis that can be overcome by CDK8/19 Mediator kinase inhibition.


ABSTRACT: Anoikis resistance or evasion of cell death triggered by cell detachment into suspension is a hallmark of cancer that is concurrent with cell survival and metastasis. The effects of frequent matrix detachment encounters on the development of anoikis resistance in cancer remains poorly defined. Here we show using a panel of ovarian cancer models, that repeated exposure to suspension stress in vitro followed by attached recovery growth leads to the development of anoikis resistance paralleling in vivo development of anoikis resistance in ovarian cancer ascites. This resistance is concurrent with enhanced invasion, chemoresistance and the ability of anoikis adapted cells to metastasize to distant sites. Adapted anoikis resistant cells show a heightened dependency on oxidative phosphorylation and can also evade immune surveillance. We find that such acquired anoikis resistance is not genetic, as acquired resistance persists for a finite duration in the absence of suspension stress. Transcriptional reprogramming is however essential to this process, as acquisition of adaptive anoikis resistance in vitro and in vivo is exquisitely sensitive to inhibition of CDK8/19 Mediator kinase, a pleiotropic regulator of transcriptional reprogramming. Our data demonstrate that growth after recovery from repeated exposure to suspension stress is a direct contributor to metastasis and that inhibition of CDK8/19 Mediator kinase during such adaptation provides a therapeutic opportunity to prevent both local and distant metastasis in cancer.

SUBMITTER: Monavarian M 

PROVIDER: S-EPMC10723298 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

Development of adaptive anoikis resistance promotes metastasis that can be overcome by CDK8/19 Mediator kinase inhibition.

Monavarian Mehri M   Page Emily Faith EF   Rajkarnikar Resha R   Kumari Asha A   Macias Liz Quintero LQ   Massicano Felipe F   Lee Nam Y NY   Sahoo Sarthak S   Hempel Nadine N   Jolly Mohit Kumar MK   Ianov Lara L   Worthey Elizabeth E   Singh Abhyudai A   Broude Eugenia V EV   Mythreye Karthikeyan K  

bioRxiv : the preprint server for biology 20231206


Anoikis resistance or evasion of cell death triggered by cell detachment into suspension is a hallmark of cancer that is concurrent with cell survival and metastasis. The effects of frequent matrix detachment encounters on the development of anoikis resistance in cancer remains poorly defined. Here we show using a panel of ovarian cancer models, that repeated exposure to suspension stress in vitro followed by attached recovery growth leads to the development of anoikis resistance paralleling in  ...[more]

Similar Datasets

2024-12-01 | GSE241546 | GEO
| PRJNA1008671 | ENA
| S-EPMC3734828 | biostudies-literature
| S-EPMC9371674 | biostudies-literature
| S-EPMC7407352 | biostudies-literature
| S-EPMC5726794 | biostudies-literature
| S-EPMC3648612 | biostudies-literature
| S-EPMC3898493 | biostudies-literature
| S-EPMC10714915 | biostudies-literature
| S-EPMC6167877 | biostudies-literature