期刊
NANO LETTERS
卷 19, 期 11, 页码 7691-7702出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.9b02592
关键词
KIF20A; microrheology; optical tweezers; AFM; bladder cancer; power law; cell migration
类别
资金
- MERSEC
- Physical Science Oncology Center (PSOC) [U54-CA193417]
- Labex postdoctoral fellowship
- Sorbonne Universite UPMC University Paris 06 (Programme Doctoral Interfaces Pour le Vivant)
- Agence Nationale de la Recherche (ANR)
- NIH [GM111942]
- Center for Engineering Mechanobiology [NSF STC 1548571]
- INSERM Plan Cancer 2009-2013 INSERM-CEA Tecsan [PC201125]
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.
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