Role of a Kinesin Motor in Cancer Cell Mechanics.
AFM
KIF20A
bladder cancer
cell migration
microrheology
optical tweezers
power law
Journal
Nano letters
ISSN: 1530-6992
Titre abrégé: Nano Lett
Pays: United States
ID NLM: 101088070
Informations de publication
Date de publication:
13 11 2019
13 11 2019
Historique:
pubmed:
1
10
2019
medline:
28
7
2020
entrez:
1
10
2019
Statut:
ppublish
Résumé
Molecular motors play important roles in force generation, migration, and intracellular trafficking. Changes in specific motor activities are altered in numerous diseases. KIF20A, a motor protein of the kinesin-6 family, is overexpressed in bladder cancer, and KIF20A levels correlate negatively with clinical outcomes. We report here a new role for the KIF20A kinesin motor protein in intracellular mechanics. Using optical tweezers to probe intracellular mechanics and surface AFM to probe cortical mechanics, we first confirm that bladder urothelial cells soften with an increasing cancer grade. We then show that inhibiting KIF20A makes the intracellular environment softer for both high- and low-grade bladder cancer cells. Upon inhibition of KIF20A, cortical stiffness also decreases in lower grade cells, while it surprisingly increases in higher grade malignant cells. Changes in cortical stiffness correlate with the interaction of KIF20A with myosin IIA. Moreover, KIF20A inhibition negatively regulates bladder cancer cell motility irrespective of the underlying substrate stiffness. Our results reveal a central role for a microtubule motor in cell mechanics and migration in the context of bladder cancer.
Identifiants
pubmed: 31565944
doi: 10.1021/acs.nanolett.9b02592
pmc: PMC7737127
mid: NIHMS1563270
doi:
Substances chimiques
KIF20A protein, human
0
Myosins
EC 3.6.4.1
Kinesins
EC 3.6.4.4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
7691-7702Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM111942
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA193417
Pays : United States
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