AI Article Synopsis

  • - Epithelial-to-mesenchymal transition (EMT) is a process that helps cancer cells spread (metastasize) and become resistant to cell death and treatments, but the triggers for EMT are not well understood
  • - The study shows that DNA damage activates specific proteins (PARP and ALC1), which help EMT transcription factors access DNA, leading to changes in cell behavior and enhanced ability to repair DNA
  • - Using a PARP inhibitor can reverse or prevent EMT caused by DNA damage, and help make cancer cells more sensitive to other treatments, offering potential new strategies for cancer therapy

Article Abstract

Epithelial-to-mesenchymal transition (EMT) allows cancer cells to metastasize while acquiring resistance to apoptosis and chemotherapeutic agents with significant implications for patients' prognosis and survival. Despite its clinical relevance, the mechanisms initiating EMT during cancer progression remain poorly understood. We demonstrate that DNA damage triggers EMT and that activation of poly (ADP-ribose) polymerase (PARP) and the PARP-dependent chromatin remodeler ALC1 (CHD1L) was required for this response. Our results suggest that this activation directly facilitates access to the chromatin of EMT transcriptional factors (TFs) which then initiate cell reprogramming. We also show that EMT-TFs bind to the RAD51 promoter to stimulate its expression and to promote DNA repair by homologous recombination. Importantly, a clinically relevant PARP inhibitor reversed or prevented EMT in response to DNA damage while resensitizing tumor cells to other genotoxic agents. Overall, our observations shed light on the intricate relationship between EMT, DNA damage response, and PARP inhibitors, providing potential insights for in cancer therapeutics.

Download full-text PDF

Source
http://dx.doi.org/10.1091/mbc.E24-08-0370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656468PMC

Publication Analysis

Top Keywords

dna damage
12
parp-dependent chromatin
8
chromatin remodeler
8
remodeler alc1
8
dna repair
8
tumor cells
8
emt
7
dna
6
dna damage-induced
4
damage-induced emt
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!