The tumor suppressor p53 can promote collective cellular migration

Loss of function of the tumor suppressor p53 is known to increase the rate of migration of cells transiting the narrow pores of the traditional Boyden chamber assay. Here by contrast we investigate how p53 impacts the rate of cellular migration within a 2D confluent cell layer and a 3D collagen-embe...

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Bibliographic Details
Published in:PloS one 2019-02, Vol.14 (2), p.e0202065-e0202065
Main Authors: He, Shijie, Carman, Christopher V, Lee, Jung Hyun, Lan, Bo, Koehler, Stephan, Atia, Lior, Park, Chan Young, Kim, Jae Hun, Mitchel, Jennifer A, Park, Jin-Ah, Butler, James P, Lu, Quan, Fredberg, Jeffrey J
Format: Article
Language:English
Subjects:
Actin
Biology
Biology and Life Sciences
Bladder
Bladder cancer
Boyden chamber
Brain
Cancer
Carcinoma
Cell adhesion & migration
Cell Line, Tumor
Cell migration
Cell Movement - physiology
Collagen
Collagen - metabolism
Collagens
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - metabolism
Colorectal Neoplasms - pathology
Cortex
Diffusion rate
HCT116 Cells
Health aspects
Humans
Kinases
Lamellipodia
Mechanics
Medicine and Health Sciences
Metastasis
Microenvironments
Motility
Muscle proteins
Null cells
p53 Protein
Physical Sciences
Polarity
Proteins
Pseudopodia
Public health
Research and Analysis Methods
Spheroids, Cellular
Substrates
Traction force
Tumor cell lines
Tumor Microenvironment
Tumor proteins
Tumor suppressor genes
Tumor Suppressor Protein p53 - metabolism
Tumors
Urinary Bladder Neoplasms - metabolism
Urinary Bladder Neoplasms - pathology
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Summary:Loss of function of the tumor suppressor p53 is known to increase the rate of migration of cells transiting the narrow pores of the traditional Boyden chamber assay. Here by contrast we investigate how p53 impacts the rate of cellular migration within a 2D confluent cell layer and a 3D collagen-embedded multicellular spheroid. We use two human carcinoma cell lines, the bladder carcinoma EJ and the colorectal carcinoma HCT116. In the confluent 2-D cell layer, for both EJ and HCT cells the migratory speeds and effective diffusion coefficients for the p53 null cells were significantly smaller than in p53-expressing cells. Compared to p53 expressers, p53-null cells exhibited more organized cortical actin rings together with reduced front-rear cell polarity. Furthermore, loss of p53 caused cells to exert smaller traction forces upon their substrates, and reduced formation of cryptic lamellipodia. In the 3D multicellular spheroid, loss of p53 consistently reduced collective cellular migration into surrounding collagen matrix. As regards the role of p53 in cellular migration, extrapolation from the Boyden chamber assay to other cellular microenvironments is seen to be fraught even in terms of the sign of the effect. Together, these paradoxical results show that the effects of p53 on cellular migration are context-dependent.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0202065