APC-driven actin nucleation powers collective cell dynamics in colorectal cancer cells

Lautaro Baro; Asifa Islam; Hannah M Brown; Zoë A Bell; M Angeles Juanes

doi:10.1016/j.isci.2023.106583

APC-driven actin nucleation powers collective cell dynamics in colorectal cancer cells

iScience. 2023 Apr 6;26(5):106583. doi: 10.1016/j.isci.2023.106583. eCollection 2023 May 19.

Authors

Lautaro Baro^{1

2}, Asifa Islam^{1

2}, Hannah M Brown^{1

2}, Zoë A Bell^{1

2}, M Angeles Juanes^{1

2

3}

Affiliations

¹ School of Health and Life Sciences, Teesside University, TS1 3BX Middlesbrough, UK.
² National Horizons Centre, Teesside University, DL1 1HG Darlington, UK.
³ Centro de Investigación Príncipe Felipe, 46012 Valencia, Spain.

Abstract

Cell remodeling relies on dynamic rearrangements of cell contacts powered by the actin cytoskeleton. The tumor suppressor adenomatous polyposis coli (APC) nucleate actin filaments (F-actin) and localizes at cell junctions. Whether APC-driven actin nucleation acts in cell junction remodeling remains unknown. By combining bioimaging and genetic tools with artificial intelligence algorithms applied to colorectal cancer cell, we found that the APC-dependent actin pool contributes to sustaining levels of F-actin, as well as E-cadherin and occludin protein levels at cell junctions. Moreover, this activity preserved cell junction length and angle, as well as vertex motion and integrity. Loss of this F-actin pool led to larger cells with slow and random cell movement within a sheet. Our findings suggest that APC-driven actin nucleation promotes cell junction integrity and dynamics to facilitate collective cell remodeling and motility. This offers a new perspective to explore the relevance of APC-driven cytoskeletal function in gut morphogenesis.

Keywords: Cancer; Cell biology.