Mitotic centromere-associated kinesin (MCAK/KIF2C) regulates cell migration and invasion by modulating microtubule dynamics and focal adhesion turnover

  • 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.

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Author:Ha Hyung Moon, Nina-Naomi KreisORCiDGND, Alexandra Friemel, Susanne Roth, Dorothea SchulteORCiDGND, Christine SolbachORCiDGND, Frank LouwenORCiDGND, Juping YuanORCiDGND, Andreas Hans RitterORCiDGND
URN:urn:nbn:de:hebis:30:3-823739
DOI:https://doi.org/10.3390/cancers13225673
ISSN:2072-6694
Parent Title (English):Cancers
Publisher:MDPI
Place of publication:Basel
Document Type:Article
Language:English
Date of Publication (online):2021/11/12
Date of first Publication:2021/11/12
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2024/02/22
Tag:CRISPR/dCas9; MCAK; actin cytoskeleton; depolymerization; focal adhesion; invasion; microtubule dynamics; migration; motility; plus-tip
Volume:13
Issue:22, art. 5673
Article Number:5673
Page Number:24
First Page:1
Last Page:24
Note:
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.
HeBIS-PPN:522324355
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International