The aper presents research demonstrating that changes in the extracellular matrix (ECM) viscoelasticity, specifically caused by Advanced Glycation End-products (AGEs), promote the progression of liver cancer (hepatocellular carcinoma or HCC) in pre-cirrhotic conditions, independent of matrix stiffness. The accumulation of AGEs, a characteristic of Type 2 diabetes mellitus (T2DM) and non-alcoholic steatohepatitis (NASH), modifies collagen architecture, enhancing the liver's viscoelastic properties by promoting faster stress relaxation. Mechanistically, this high viscoelasticity activates a pro-tumorigenic pathway involving Integrin-β1, Tensin-1 (TNS1), and the YAP mechanotransductive pathway, leading to increased HCC cell proliferation and invasion. Furthermore, experimental interventions that reduce AGEs or break AGE-collagen cross-links diminish viscoelasticity and suppress tumor growth, suggesting that targeting viscoelasticity could offer novel diagnostic and therapeutic strategies for T2DM/NASH-related HCC.

References:

• Fan W, Adebowale K, Vancza L, et al. Matrix viscoelasticity promotes liver cancer progression in the pre-cirrhotic liver[J]. Nature, 2024, 626(7999): 635-642.