Mechanobiological reprogramming in liver cancer: Conjugated linoleic acid disrupts EMT and cytoskeletal dynamics

Abstract

The excessive increase in hepatocellular carcinoma (HCC) incidence and poor therapeutic responses have led researchers to focus on innovative approaches like differentiation therapy. An anticancer agent, conjugated linoleic acid (CLA), can induce differentiation and inhibit epithelial-mesenchymal transition (EMT) in HCC cells through the upregulation of hepatocyte nuclear factor 4 alpha (HNF4α). This study aims to investigate the mechanobiological alterations, which are important in metastasis, in HCC cells after CLA treatment. Hep3B cells were treated with different concentrations of CLA. The morphology, viability, migration ability, and variation in the density and localization of the cell’s cytoskeleton filaments (CSFs) were evaluated. Then, the induction of epithelial morphology in the cells was quantified using different geometric criteria. Finally, the effect of CLA treatment on the elastic and viscoelastic properties of the cells was investigated. CLA treatment suppressed the individual and collective migration of HCC cells and reduced their dynamic movements. With increasing concentrations of CLA, the ratio of the relative fluorescent of the filaments (RFF) decreased in the nucleus and increased in cytoplasm areas. However, the expression of vimentin in all parts of the cells was remarkably reduced. Additionally, CLA treatment increased the epithelial characteristics of the HCC cells from the morphological perspective and improved their viscoelastic properties. CLA treatment reduced the cancerous characteristics of HCC cells and inhibited the EMT process by strengthening the mechanobiological features and rearranging their cytoskeleton network.