How HMTs regulate signalling pathways for cytoskeleton, cell shape and cell migration
Attainment of proper cell shape and regulation of cell migration are essential processes in development of an organism. Same processes, if deregulated, are associated with disease conditions like chronic inflammation and cancer metastasis. In an ongoing study in the lab, we report that loss of MLL results in abnormal cell shape and disrupted actin cytoskeleton which leads to diminished cell spreading and migration. We uncover the role of MLL in regulation of homeostasis of key small Rho GTPases.
Cell migration is of paramount importance for cancer progression. A tremendous amount of research has been dedicated to find targets that would stop cancer cell to metastasis. Based on our studies, we propose MLL as a novel therapeutic target for treating triple negative breast cancer and other cancers showing over-expression of Rho GTPases. Our studies highlight the central regulatory role of MLL in Rho GTPases signalling pathways.
Loss of MLL results in impaired actin stress fiber formation.
Cells show actin stress fibers upon staining with phalloidin peptide (see Control). These actin stress fibers are one of the key determinants of cell shape and cell migration. Upon treatment with MLL siRNA, the actin stress fibers are lost. Also note the shape of cell in presence and absence of MLL and formation of small protrusions in latter.