Generation of anisotropic strain dysregulates wild-type cell division at the interface between host and oncogenic tissue

Curr Biol. 2021 Jun 3:S0960-9822(21)00712-0. doi: 10.1016/j.cub.2021.05.023. Online ahead of print.ABSTRACTEpithelial tissues are highly sensitive to anisotropies in mechanical force, with cells altering fundamental behaviors, such as cell adhesion, migration, and cell division.1-5 It is well known that, in the later stages of carcinoma (epithelial cancer), the presence of tumors alters the mechanical properties of a host tissue and that these changes contribute to disease progression.6-9 However, in the earliest stages of carcinoma, when a clonal cluster of oncogene-expressing cells first establishes in the epithelium, the extent to which mechanical changes alter cell behavior in the tissue as a whole remains unclear. This is despite knowledge that many common oncogenes, such as oncogenic Ras, alter cell stiffness and contractility.10-13 Here, we investigate how mechanical changes at the cellular level of an oncogenic cluster can translate into the generation of anisotropic strain across an epithelium, altering cell behavior in neighboring host tissue. We generated clusters of oncogene-expressing cells within otherwise normal in vivo epithelium, using Xenopus laevis embryos. We find that cells in kRasV12, but not cMYC, clusters have increased contractility, which introduces radial stress in the tissue and deforms surrounding host cells. The strain imposed by kRasV12 clusters leads to increased cell division and altered division orientation in neighboring host tissue, effects...
Source: Current Biology - Category: Biology Authors: Source Type: research