Development of adaptive anoikis resistance promotes metastasis that can be overcome by CDK8/19 Mediator kinase inhibition DOI Creative Commons
Mehri Monavarian, Emily Faith Page, Resha Rajkarnikar

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 6, 2023

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

Language: Английский

Iron Memory inE. coli DOI Creative Commons
Souvik Bhattacharyya, Nabin Bhattarai,

Dylan M. Pfannenstiel

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 20, 2023

The importance of memory in bacterial decision-making is relatively unexplored. We show here that a prior experience swarming remembered when E. coli encounters new surface, improving its future efficiency. conducted >10,000 single-cell swarm assays to discover cells store the form cellular iron levels. This pre-exists planktonic cells, but act reinforces it. A cell with low initiates early and better swarmer, while opposite true for high iron. potential mother cell, whether or high, passed down fourth-generation daughter cells. naturally lost by seventh generation, artificially manipulating levels allows it persist much longer. mathematical model time-delay component faithfully recreates observed dynamic interconversions between different potentials. also demonstrate can integrate multiple stimuli, impacting other behaviors such as biofilm formation antibiotic tolerance.

Language: Английский

Citations

0
Development of adaptive anoikis resistance promotes metastasis that can be overcome by CDK8/19 Mediator kinase inhibition DOI Creative Commons
Mehri Monavarian, Emily Faith Page, Resha Rajkarnikar

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 6, 2023

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

Language: Английский

Citations

0