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 o...

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Autores principales:	Ha Hyung Moon, Nina-Naomi Kreis, Alexandra Friemel, Susanne Roth, Dorothea Schulte, Christine Solbach, Frank Louwen, Juping Yuan, Andreas Ritter
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	MCAK microtubule dynamics focal adhesion migration motility invasion Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/41b03c1ddb924ad2ad8985de467eae22
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spelling	oai:doaj.org-article:41b03c1ddb924ad2ad8985de467eae222021-11-25T17:02:30ZMitotic Centromere-Associated Kinesin (MCAK/KIF2C) Regulates Cell Migration and Invasion by Modulating Microtubule Dynamics and Focal Adhesion Turnover10.3390/cancers132256732072-6694https://doaj.org/article/41b03c1ddb924ad2ad8985de467eae222021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5673https://doaj.org/toc/2072-6694The 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.Ha Hyung MoonNina-Naomi KreisAlexandra FriemelSusanne RothDorothea SchulteChristine SolbachFrank LouwenJuping YuanAndreas RitterMDPI AGarticleMCAKmicrotubule dynamicsfocal adhesionmigrationmotilityinvasionNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5673, p 5673 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	MCAK microtubule dynamics focal adhesion migration motility invasion Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	MCAK microtubule dynamics focal adhesion migration motility invasion Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Ha Hyung Moon Nina-Naomi Kreis Alexandra Friemel Susanne Roth Dorothea Schulte Christine Solbach Frank Louwen Juping Yuan Andreas Ritter Mitotic Centromere-Associated Kinesin (MCAK/KIF2C) Regulates Cell Migration and Invasion by Modulating Microtubule Dynamics and Focal Adhesion Turnover
description	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.
format	article
author	Ha Hyung Moon Nina-Naomi Kreis Alexandra Friemel Susanne Roth Dorothea Schulte Christine Solbach Frank Louwen Juping Yuan Andreas Ritter
author_facet	Ha Hyung Moon Nina-Naomi Kreis Alexandra Friemel Susanne Roth Dorothea Schulte Christine Solbach Frank Louwen Juping Yuan Andreas Ritter
author_sort	Ha Hyung Moon
title	Mitotic Centromere-Associated Kinesin (MCAK/KIF2C) Regulates Cell Migration and Invasion by Modulating Microtubule Dynamics and Focal Adhesion Turnover
title_short	Mitotic Centromere-Associated Kinesin (MCAK/KIF2C) Regulates Cell Migration and Invasion by Modulating Microtubule Dynamics and Focal Adhesion Turnover
title_full	Mitotic Centromere-Associated Kinesin (MCAK/KIF2C) Regulates Cell Migration and Invasion by Modulating Microtubule Dynamics and Focal Adhesion Turnover
title_fullStr	Mitotic Centromere-Associated Kinesin (MCAK/KIF2C) Regulates Cell Migration and Invasion by Modulating Microtubule Dynamics and Focal Adhesion Turnover
title_full_unstemmed	Mitotic Centromere-Associated Kinesin (MCAK/KIF2C) Regulates Cell Migration and Invasion by Modulating Microtubule Dynamics and Focal Adhesion Turnover
title_sort	mitotic centromere-associated kinesin (mcak/kif2c) regulates cell migration and invasion by modulating microtubule dynamics and focal adhesion turnover
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/41b03c1ddb924ad2ad8985de467eae22
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Mitotic Centromere-Associated Kinesin (MCAK/KIF2C) Regulates Cell Migration and Invasion by Modulating Microtubule Dynamics and Focal Adhesion Turnover

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