Biomol Ther.  2015 Jul;23(4):301-312. 10.4062/biomolther.2015.032.

Phosphorylation and Reorganization of Keratin Networks: Implications for Carcinogenesis and Epithelial Mesenchymal Transition

• Kim HJ
• Choi WJ
• Lee CH

• KMID: 2382358
• DOI: http://doi.org/10.4062/biomolther.2015.032

Abstract

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.

Keyword

Metastasis; Viscoelasticity; Phosphorylation of keratin; Reorganization of keratin; Epithelial Mesenchymal Transition; Sphingosylphosphorylcholine

MeSH Terms

Carcinogenesis*
Cell Membrane
Epithelial-Mesenchymal Transition*
Humans
Intermediate Filaments
Neoplasm Metastasis
Phosphoprotein Phosphatases
Phosphorylation*
Phosphotransferases
Phosphoprotein Phosphatases
Phosphotransferases