Interaction between m6A and YAP1 mechanotransduction pathways is essential for mechanical memory and matrix remodeling in pancreatic cancer - PubMed
2 days ago
- #Pancreatic Cancer
- #Mechanical Memory
- #Matrix Remodeling
- Pancreatic cancer's aggressive nature is linked to a stiffened extracellular matrix, promoting mechanical memory in cancer cells and aiding in malignant progression and metastasis.
- High-stiffness microenvironments induce mechanical memory in pancreatic tumor cells, worsening stromal remodeling and prognosis.
- Under stiff conditions, pancreatic cancer cells show increased m6A levels and enrichment in RNA modification-related and metabolic pathways.
- A METTL14-YAP1 feedback loop is identified, where METTL14 enhances YAP1 expression via YTHDF3-mediated m6A-dependent regulation, and YAP1 upregulates METTL14 transcriptionally through TEAD1.
- This METTL14-YAP1 axis activates the CD166-EGFR-LOXL2 signaling pathway, leading to increased collagen cross-linking, stromal stiffness, and tumor stemness maintenance.
- Targeting the METTL14-YAP1 feedback loop is suggested as a potential therapeutic strategy to disrupt mechanical memory and reduce stiffness-induced remodeling in pancreatic cancer.