Mechanisms of the MRTF-A controlled myofibroblastic differentiation and its influence on the tumour propagating function of mesenchymal stromal cells

Abstract

MRTF-A is a key transcriptional regulator of myofibroblastic differentiation. This thesis investigates its role in primary human mesenchymal stromal cells (MSCs) in colorectal cancer. TGF-β1, secreted by colorectal cancer cells such as HCT-8, activates MRTF-A, driving the expression of contractile and extracellular matrix genes and establishing a distinct myofibroblastic signature. These changes resemble features of cancer-associated fibroblasts (CAFs). Functionally, MRTF-A enhances the tumour-supportive phenotype of MSCs, as shown in vitro and in a colorectal cancer xenograft model. MRTF-A depletion via siRNA and shRNA reduces both myofibroblastic traits and pro-tumourigenic effects, underscoring MRTF-A as a central mediator of TGF-β–driven stromal activation.