PgmNr D1098: Investigating the role of epithelial curvature in growth control.

Authors:
Lina ZHANG 1,2 ; Tiantian JI 1,2 ; Xianwei CHEN 1,2 ; Hongkai LIU 1,2 ; Yan YAN 1,2


Institutes
1) HKUST, Division of Life Science, Hong Kong, China; 2) HKUST, Center for Systems Biology and Human Health, Hong Kong, China.


Keyword: tissue growth

Abstract:

Epithelial cells are highly polarized cells with distinct apical and basolateral domains defined by specific protein complexes. The conserved Scribble module localizes at the basolateral region. It consists of three scaffold proteins, namely Scribble (Scrib), Discs large (Dlg) and Lethal giant larvae (Lgl). The Scribble module was originally identified in Drosophila as a group of “neoplastic tumor suppressor genes” (nTSGs). Drosophila imaginal disc cells homozygous mutant for the Scribble module genes grow into tumors that are disorganized, undifferentiated, lethal and transplantable. In mammals, loss of the Scribble module function is also linked with epithelial tumor progression.

We noticed that the cells deficient for the Scribble module show location-dependent growth phenotypes. Specifically, the Scrib and Dlg deficient cells can only grow into tumor-like masses in the highly curved epithelial regions including the hinge region of wing imaginal discs and the polar region of the follicular epithelia. We found that the ectopic activation of myosin II activity induces folding in the flat wing pouch region and rescues the Scrib and Dlg deficient cells from cell competition-induced elimination. The folded wing hinge region exhibits higher Yki activity. Moreover, MDCK and MCF10A cells cultured on curved surfaces display differential YAP/TAZ activity correlating with the substrate curvature. These data indicate that the curvature might play a role in modulating the epithelial baseline Yki activity and thus influence the growth outcome of the nTSG mutant cells.