Open AccessRole of a Kinesin Motor in Cancer Cell Mechanics
Author(s) -
Kalpana Mandal,
Katarzyna Pogoda,
Satabdi Nandi,
Samuel Mathieu,
Amal Kasri,
Eric A. Klein,
François Radvanyi,
Bruno Goud,
Paul A. Janmey,
JeanBaptiste Manneville
Publication year - 2019
Publication title -
nano letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.853
H-Index - 488
eISSN - 1530-6992
pISSN - 1530-6984
DOI - 10.1021/acs.nanolett.9b02592
Subject(s) - kinesin , intracellular , bladder cancer , cancer cell , motor protein , context (archaeology) , motility , molecular motor , microtubule , stiffness , myosin , biophysics , nanotechnology , microbiology and biotechnology , cancer , materials science , chemistry , biology , medicine , paleontology , composite material
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.