RT Journal Article
SR Electronic
T1 The tumor suppressor p53 promotes carcinoma invasion and collective cellular migration
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 380600
DO 10.1101/380600
A1 Shijie He
A1 Christopher V. Carman
A1 Jung Hyun Lee
A1 Bo Lan
A1 Stephan Koehler
A1 Lior Atia
A1 Chan Young Park
A1 Jae Hun Kim
A1 Jennifer A. Mitchel
A1 Jin-Ah Park
A1 James P. Butler
A1 Sam W. Lee
A1 Jeffrey J. Fredberg
YR 2018
UL http://biorxiv.org/content/early/2018/07/30/380600.abstract
AB Summary Loss of function of the tumor suppressor p53 is generally thought to increase cell motility and invasiveness. Using 2-D confluent and 3-D spheroidal cell motility assays with bladder carcinoma cells and colorectal carcinoma cells, we report, to the contrary, that loss of p53 can decrease cell motility and invasion.Abstract For migration of the single cell studied in isolation, loss of function of the tumor suppressor p53 is thought to increase cell motility. Here by contrast we used the 2-D confluent cell layer and the 3-D multicellular spheroid to investigate how p53 impacts dissemination and invasion of cellular collectives. We used two human carcinoma cell lines, the bladder carcinoma EJ and the colorectal carcinoma HCT116. We began by replicating single cell invasion in the traditional Boyden chamber assay, and found that the number of invading cells increased with loss of p53, as expected. In the confluent 2-D cell layer, however, for both EJ and HCT, speeds and effective diffusion coefficients for the p53 null types compared to their p53 expressing counterparts were significantly smaller. 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 a 3-D collagen matrix, p53 consistently promoted invasion of the multicellular spheroids into surrounding matrix. Together, these results show that p53 expression in these carcinoma model systems increases collective cellular migration and invasion. As such, these studies point to paradoxical contributions of p53 in single cell versus collective cellular migration.