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Dev Cell. 2018 Oct 22;47(2):161-174.e4. doi: 10.1016/j.devcel.2018.08.021. Epub 2018 Sep 20.

Chromosomal Instability Induces Cellular Invasion in Epithelial Tissues.

Author information

1
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac 10-12, Barcelona 08028, Spain.
2
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac 10-12, Barcelona 08028, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Passeig Lluís Companys 23, Barcelona 08010, Spain. Electronic address: marco.milan@irbbarcelona.org.

Abstract

Most sporadic carcinomas with high metastatic activity show an increased rate of changes in chromosome structure and number, known as chromosomal instability (CIN). However, the role of CIN in driving invasiveness remains unclear. Using an epithelial model in Drosophila, we present evidence that CIN promotes a rapid and general invasive behavior. Cells with an abnormal number of chromosomes delaminate from the epithelium, extend actin-based cellular protrusions, form membrane blebs, and invade neighboring tissues. This behavior is governed by the activation of non-muscle Myosin II by Rho kinase and by the expression of the secreted EGF/Spitz ligand. We unravel fundamental roles of the mitogen-activated protein kinase pathways mediated by the Fos proto-oncogene and the Capicua tumor suppressor gene in the invasive behavior of CIN-induced aneuploid cells. Our results support the proposal that the simple production of unbalanced karyotypes contributes to CIN-induced metastatic progression.

KEYWORDS:

Capicua; Drosophila; EGFR; Fos; JNK; Myosin II; blebbing; cell invasion; chromosomal instability; gene dosage imbalance

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