Disruption of thrombospondin 1/2-integrin β1 axis impairs cell adhesion and tumor growth in intrahepatic cholangiocarcinoma - PubMed
3 hours ago
- #cell-adhesion
- #cancer-biology
- #therapeutic-targets
- Thrombospondin 1 (THBS1) and 2 (THBS2) are highly expressed in intrahepatic cholangiocarcinoma (iCCA) and promote tumor growth and metastasis.
- These proteins are mainly produced by cancer-associated fibroblasts (CAFs) and iCCA cells, enhancing malignant cell interaction with the extracellular matrix (ECM).
- Integrin α3β1 and α6β1 are identified as receptors for THBS1 and THBS2 on iCCA cells.
- Disrupting the THBS1-integrin β1 axis with antibodies, peptides, or knockout reduces integrin β1 activation and ECM adhesion in 2D and 3D assays.
- Loss of THBS1 alters cell morphology, weakens junctions, and prevents tumor formation in mouse models, highlighting this axis as a therapeutic target.