A Soft Matrix Microenvironment Promotes Laterally Spreading Tumors via Oxidative Phosphorylation-Dependent Cell Adhesion - PubMed
4 hours ago
- #tumor microenvironment
- #colorectal neoplasms
- #oxidative phosphorylation
- Laterally spreading tumors (LSTs) are large, flat, early-stage precancerous colorectal lesions that are frequently overlooked during endoscopic examination.
- LSTs exhibit a more malignant phenotype compared to conventional protruding adenomas (PAs), with high copy number variation (CNV) scores and stronger genetic correlation with colorectal cancer.
- LSTs show downregulation of adhesion molecules, associated with cytoskeletal depolymerization and enhanced oxidative phosphorylation (OXPHOS).
- LSTs reside in a softer extracellular matrix than PAs, which promotes OXPHOS and modulates adhesion via the ENTPD1-ADORA2B axis.
- A mechanochemical model is proposed where a soft matrix is coupled with OXPHOS and cytoskeletal remodeling through ENTPD1-ADORA2B, coinciding with adhesion suppression.
- The findings highlight the ENTPD1-ADORA2B axis as a potential target for future mechanistic investigation in LST lateral growth.