Cytoskeletal Dynamics in Epithelial-Mesenchymal Transition: Insights into Therapeutic Targets for Cancer Metastasis.
Arpita DattaShuo DengVennila GopalKenneth Chun-Hong YapClarissa Esmeralda HalimMun Leng LyeMei Shan OngTuan-Zea TanGautam SethiShing Chuan HooiAlan Prem KumarCelestial T YapPublished in: Cancers (2021)
In cancer cells, a vital cellular process during metastasis is the transformation of epithelial cells towards motile mesenchymal cells called the epithelial to mesenchymal transition (EMT). The cytoskeleton is an active network of three intracellular filaments: actin cytoskeleton, microtubules, and intermediate filaments. These filaments play a central role in the structural design and cell behavior and are necessary for EMT. During EMT, epithelial cells undergo a cellular transformation as manifested by cell elongation, migration, and invasion, coordinated by actin cytoskeleton reorganization. The actin cytoskeleton is an extremely dynamic structure, controlled by a balance of assembly and disassembly of actin filaments. Actin-binding proteins regulate the process of actin polymerization and depolymerization. Microtubule reorganization also plays an important role in cell migration and polarization. Intermediate filaments are rearranged, switching to a vimentin-rich network, and this protein is used as a marker for a mesenchymal cell. Hence, targeting EMT by regulating the activities of their key components may be a potential solution to metastasis. This review summarizes the research done on the physiological functions of the cytoskeleton, its role in the EMT process, and its effect on multidrug-resistant (MDR) cancer cells-highlight some future perspectives in cancer therapy by targeting cytoskeleton.
Keyphrases
- epithelial mesenchymal transition
- cell migration
- multidrug resistant
- cancer therapy
- transforming growth factor
- single cell
- cell therapy
- signaling pathway
- stem cells
- bone marrow
- induced apoptosis
- squamous cell carcinoma
- oxidative stress
- cystic fibrosis
- drug resistant
- drug delivery
- cell proliferation
- papillary thyroid
- squamous cell
- escherichia coli
- gram negative
- mesenchymal stem cells
- reactive oxygen species
- binding protein
- risk assessment
- endoplasmic reticulum stress