Tankyrase inhibition impairs directional migration and invasion of lung cancer cells by affecting microtubule dynamics and polarity signals

BMC Biology
Barbara LupoLivio Trusolino

Abstract

Tankyrases are poly(adenosine diphosphate)-ribose polymerases that contribute to biological processes as diverse as modulation of Wnt signaling, telomere maintenance, vesicle trafficking, and microtubule-dependent spindle pole assembly during mitosis. At interphase, polarized reshaping of the microtubule network fosters oriented cell migration. This is attained by association of adenomatous polyposis coli with the plus end of microtubules at the cortex of cell membrane protrusions and microtubule-based centrosome reorientation towards the migrating front. Here we report a new function for tankyrases, namely, regulation of directional cell locomotion. Using a panel of lung cancer cell lines as a model system, we found that abrogation of tankyrase activity by two different, structurally unrelated small-molecule inhibitors (one introduced and characterized here for the first time) or by RNA interference-based genetic silencing weakened cell migration, invasion, and directional movement induced by the motogenic cytokine hepatocyte growth factor. Mechanistically, the anti-invasive outcome of tankyrase inhibition could be ascribed to sequential deterioration of the distinct events that govern cell directional sensing. In particular, ...Continue Reading

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Citations

Oct 23, 2019·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Meng ZhangQiang Wang
Oct 28, 2019·Anti-cancer Agents in Medicinal Chemistry·Xylia Q PetersMahmoud E S Soliman
Mar 9, 2019·Biomolecular NMR Assignments·Mariola ZaleskaMark Pfuhl
Nov 23, 2019·Cellular and Molecular Life Sciences : CMLS·Travis Eisemann, John M Pascal
May 1, 2021·International Journal of Molecular Sciences·Gleb SimanovAlexis M Gautreau
Aug 21, 2021·International Journal of Pharmaceutics·Tongyu LiHangxiang Wang

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Methods Mentioned

BETA
transfection

Software Mentioned

LAS AF Leica Application Suite
Graphpad Quickcalcs
Leica
MATLAB
ImageJ

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