Metastasis is one of hallmarks of
cancer and a major cause of
cancer death. Combatting
metastasis is highly challenging. To overcome these difficulties, researchers have focused on physical properties of metastatic
cancer cells. Metastatic
cancer cells from patients are softer than benign
cancer or normal cells. Changes of viscoelasticity of
cancer cells are related to the
keratin network. Unexpectedly,
keratin network is dynamic and regulation of
keratin network is important to the
metastasis of
cancer.
Keratin is composed of heteropolymer of type I and II.
Keratin connects from the plasma membrane to nucleus. Several
proteins including
kinases, and
protein phosphatases bind to
keratin intermediate filaments. Several endogenous compounds or toxic compounds induce phosphorylation and reorganization of
keratin network in
cancer cells, leading to increased migration. Continuous phosphorylation of
keratin results in loss of
keratin, which is one of the features of epithelial mesenchymal transition (EMT). Therefore, several
proteins involved in phosphorylation and reorganization of
keratin also have a role in EMT. It is likely that compounds controlling phosphorylation and reorganization of
keratin are potential candidates for combating EMT and
metastasis.