Congrats to Johnson and the team! Our paper “Chemotherapy enriched THBS2-deficient cancer stem cells drive hepatocarcinogenesis through matrix softness induced histone H3 modifications” is accepted for publication in Advanced Science.
Findings of this study show that extracellular matrix remodeling by chemotherapy 5-FU enriched THBS2-deficient CD133 cancer stem cells can provide a route of escape that leads to HCC metastasis. In brief, 5-FU enriches for CD133 expressing cells with deficient THBS2 expression. THBS2, which is a known extracellular matrix (ECM)-modifying protein, has the ability to alter MMP2/MMP9 activity and thus collagen and matrix stiffness, which leads to altered cancer and stemness properties. This local soft microenvironment then induces mechano-epigenetic changes to enhance CD133 expression and suppress THBS2 expression through histone H3 modifications at their respective promoter regions, facilitating a positive feedback loop that supports the clonogenic expansion of a subpopulation of HCC cells with high CD133 expression and low THBS2 expression.