TY  - JOUR
A1  - Moon, Ha Hyung
A1  - Kreis, Nina-Naomi
A1  - Friemel, Alexandra
A1  - Roth, Susanne
A1  - Schulte, Dorothea
A1  - Solbach, Christine
A1  - Louwen, Frank
A1  - Yuan, Juping
A1  - Ritter, Andreas Hans
T1  - Mitotic centromere-associated kinesin (MCAK/KIF2C) regulates cell migration and invasion by modulating microtubule dynamics and focal adhesion turnover
T2  - Cancers
N2  - The microtubule (MT) cytoskeleton is crucial for cell motility and migration by regulating multiple cellular activities such as transport and endocytosis of key components of focal adhesions (FA). The kinesin-13 family is important in the regulation of MT dynamics and the best characterized member of this family is the mitotic centromere-associated kinesin (MCAK/KIF2C). Interestingly, its overexpression has been reported to be related to increased metastasis in various tumor entities. Moreover, MCAK is involved in the migration and invasion behavior of various cell types. However, the precise molecular mechanisms were not completely clarified. To address these issues, we generated CRISPR/dCas9 HeLa and retinal pigment epithelium (RPE) cell lines overexpressing or downregulating MCAK. Both up- or downregulation of MCAK led to reduced cell motility and poor migration in malignant as well as benign cells. Specifically, it’s up- or downregulation impaired FA protein composition and phosphorylation status, interfered with a proper spindle and chromosome segregation, disturbed the assembly and disassembly rate of FA, delayed cell adhesion, and compromised the plus-tip dynamics of MTs. In conclusion, our data suggest MCAK act as an important regulator for cell motility and migration by affecting the actin-MT cytoskeleton dynamics and the FA turnover, providing molecular mechanisms by which deregulated MCAK could promote malignant progression and metastasis of tumor cells.
KW  - MCAK
KW  - microtubule dynamics
KW  - focal adhesion
KW  - migration
KW  - motility
KW  - invasion
KW  - plus-tip
KW  - actin cytoskeleton
KW  - depolymerization
KW  - CRISPR/dCas9
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/82373
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-823739
SN  - 2072-6694
N1  - This project was partially funded by the “Deutsche Forschungsgemeinschaft” (DFG, German Research Foundation, project number 413992926) and supported by a young investigator grant of the Frankfurt Research Promotion Program (FFF) of the Faculty of Medicine at Goethe University.
VL  - 13
IS  - 22, art. 5673
SP  - 1
EP  - 24
PB  - MDPI
CY  - Basel
ER  -