Dysregulated wild-type cell division at the interface between host and oncogenic epithelium [article]

Megan Moruzzi, Alexander Nestor-Bergmann, Keith Brennan, Sarah Woolner
2019 bioRxiv   pre-print
Carcinomas dysregulate their microenvironment and this helps aid disease progression, in part by altering the behaviour of host cells from different lineages, such as immune and endothelial cells. However, it remains largely unknown whether small groups of cells with initial oncogenic changes alter their environment or affect fundamental processes, such as cell division, in host epithelia. In this study, clusters of oncogene-expressing cells were created within otherwise normal, in vivo tissue,
more » ... al, in vivo tissue, using Xenopus embryos. We find that clusters overexpressing kRasV12 or cMYC significantly increase cell division in neighbouring host epithelium. Furthermore, we show that hyper-contractility of kRasV12 clusters generates forces that deform host epithelia, increasing cell division and biasing division orientation. Contrastingly, cMYC clusters do not induce deformation of surrounding tissue but drive host cell division via a distinct mechanism. Our results indicate novel roles for kRasV12 and cMYC, dysregulating cell division in surrounding host, as well as oncogene-expressing, epithelium.
doi:10.1101/578146 fatcat:tl2asjgqo5cbxj6bg2ia2hhaji