Logo image
Back
Activating the nuclear piston mechanism of 3D migration in tumor cells
Journal article   Open access   Peer reviewed

Activating the nuclear piston mechanism of 3D migration in tumor cells

Ryan J Petrie, Heather M Harlin, Lulu I T Korsak and Kenneth M Yamada
The Journal of cell biology, v 216(1), pp 93-100
02 Jan 2017
DOI: https://doi.org/10.1083/jcb.201605097
PMID: 27998990
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1083/jcb.201605097View
Published, Version of Record (VoR)CC BY-NC-SA V4.0,  Open

Abstract

Actomyosin - metabolism Cell Adhesion Cell Line, Tumor Cell Movement - drug effects Cell Nucleus - drug effects Cell Nucleus - metabolism Cell Nucleus - pathology Cell Polarity Cell Shape Fibroblasts - drug effects Fibroblasts - metabolism Fibroblasts - pathology Fibrosarcoma - genetics Fibrosarcoma - metabolism Fibrosarcoma - pathology Humans Integrins - metabolism Male Matrix Metalloproteinase 14 - genetics Matrix Metalloproteinase 14 - metabolism Matrix Metalloproteinase Inhibitors - pharmacology Mechanotransduction, Cellular - drug effects Microfilament Proteins - genetics Microfilament Proteins - metabolism Microscopy, Fluorescence Neoplasm Invasiveness Pressure Primary Cell Culture Protease Inhibitors - pharmacology Pseudopodia - metabolism Pseudopodia - pathology Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - metabolism RNA Interference Stress, Mechanical Time Factors Transfection
Primary human fibroblasts have the remarkable ability to use their nucleus like a piston, switching from low- to high-pressure protrusions in response to the surrounding three-dimensional (3D) matrix. Although migrating tumor cells can also change how they migrate in response to the 3D matrix, it is not clear if they can switch between high- and low-pressure protrusions like primary fibroblasts. We report that unlike primary fibroblasts, the nuclear piston is not active in fibrosarcoma cells. Protease inhibition rescued the nuclear piston mechanism in polarized HT1080 and SW684 cells and generated compartmentalized pressure. Achieving compartmentalized pressure required the nucleoskeleton-cytoskeleton linker protein nesprin 3, actomyosin contractility, and integrin-mediated adhesion, consistent with lobopodia-based fibroblast migration. In addition, this activation of the nuclear piston mechanism slowed the 3D movement of HT1080 cells. Together, these data indicate that inhibiting protease activity during polarized tumor cell 3D migration is sufficient to restore the nuclear piston migration mechanism with compartmentalized pressure characteristic of nonmalignant cells.

Metrics

26 Record Views
90 citations in Web of Science
89 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Collaboration types
Domestic collaboration
Web of Science research areas
Cell Biology
Logo image