RT Journal Article
SR Electronic
T1 Basal extrusion drives cell invasion and mechanical stripping of E-cadherin
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 463646
DO 10.1101/463646
A1 John Fadul
A1 Gloria M. Slattum
A1 Nadja M. Redd
A1 Mauricio Franco Jin
A1 Michael J. Redd
A1 Stephan Daetwyler
A1 Danielle Hedeen
A1 Jan Huisken
A1 Jody Rosenblatt
YR 2018
UL http://biorxiv.org/content/early/2018/11/06/463646.abstract
AB Metastasis is the predominant reason that patients succumb to cancer, yet the mechanisms that drive initial tumor cell invasion are poorly understood. We previously discovered that crowding-induced apical extrusion drives most epithelial cell death, critical to maintaining constant cell densities. Oncogenic mutations can disrupt apical cell extrusion, instead causing masses to form and aberrant basal extrusion. Using transparent zebrafish epidermis to model simple epithelia, we can image invasion events live at high resolution. We find that KRas/p53-transformed cells form masses and, at completely independent sites, invade by basal extrusion. Basal extrusion also causes invading cells to simultaneously mechanically shed their entire apical membranes and E-cadherin. Once cells invade the underlying tissue, they migrate throughout the body, divide, enter the bloodstream, and become different cell types. KRas-transformation makes cells intrinsically invasive by increasing basal extrusion rates; collaborating mutations in p53 allow disseminated cells to survive at distant sites.