Chromosomal Instability Induces Cellular Invasion in Epithelial Tissues

Benhra, Najate; Barrio, Lara; Muzzopappa, Mariana; Milán, Marco

doi:10.1016/j.devcel.2018.08.021

Cited by 31 publications

(26 citation statements)

References 68 publications

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“…(1) Aneuploid cells formed via CIN undergo tumourigenesis via JNK signalling activation, with the delamination and invasive behaviour of the cells driven by JNK targets promoting misregulation of the actin-myosin cytoskeleton (Benhra et al, 2018).…”

Section: Pro-tumourigenic Jnk Signallingmentioning

confidence: 99%

Two-Faced: Roles of JNK Signalling During Tumourigenesis in the Drosophila Model

Marca

Richardson

2020

Front. Cell Dev. Biol.

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Section: Pro-tumourigenic Jnk Signallingmentioning

confidence: 99%

Two-Faced: Roles of JNK Signalling During Tumourigenesis in the Drosophila Model

Marca

Richardson

2020

Front. Cell Dev. Biol.

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“…Dfos's upregulation of the Filamin Cheerio is also required in tumor cells and aneuploid epithelial cells to enhance ECM breaching (Külshammer & Uhlirova, 2013;Benhra et al, 2018). Both cell types displayed enhanced levels of cortical filamentous actin, which in the tumors is concomitant with Dia upregulation (Külshammer & Uhlirova, 2013).…”

Section: A Molecular Program For Tissue Invasion That Strengthens Cormentioning

confidence: 98%

Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance

Belyaeva

Wachner

Linder

et al. 2020

Preprint

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The infiltration of immune cells into tissues underlies the establishment of tissue resident macrophages, and responses to infections and tumors. Yet the mechanisms immune cells utilize to negotiate tissue barriers in living organisms are not well understood, and a role for cortical actin has not been examined. Here we find that the tissue invasion of Drosophila macrophages, also known as plasmatocytes or hemocytes, utilizes enhanced cortical F-actin levels stimulated by the Drosophila member of the fos proto oncogene transcription factor family (Dfos, Kayak). RNA sequencing analysis and live imaging show that Dfos enhances F-actin levels around the entire macrophage surface by increasing mRNA levels of the membrane spanning molecular scaffold tetraspanin TM4SF, and the actin cross-linking filamin Cheerio which are themselves required for invasion. Cortical F-actin levels are critical as expressing a dominant active form of Diaphanous, a actin polymerizing Formin, can rescue the Dfos Dominant Negative macrophage invasion defect. In vivo imaging shows that Dfos is required to enhance the efficiency of the initial phases of macrophage tissue entry. Genetic evidence argues that this Dfos-induced program in macrophages counteracts the constraint produced by the tension of surrounding tissues and buffers the mechanical properties of the macrophage nucleus from affecting tissue entry. We thus identify tuning the cortical actin cytoskeleton through Dfos as a key process allowing efficient forward movement of an immune cell into surrounding tissues.

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“…Normal cells detect and repair DNA damage, ensuring the maintenance of the correct number of chromosomes and tissue homeostasis, instead often cancer cells have increased mutation-rates leading to high chromosomal instability (CIN) that triggers aneuploidy and advances tumorigenesis (Negrini et al, 2010). Chromosomal instability is a process conserved also in Drosophila , and it was shown to contribute to the invasive behavior of epithelial cells, with a mechanism called “compensatory proliferation” activated to counteract CIN-induced cell death (Clemente-Ruiz et al, 2016; Benhra et al, 2018).…”

Section: Cancer and Immune Systemmentioning

confidence: 99%

Drosophila melanogaster: A Model Organism to Study Cancer

et al. 2019

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Cancer is a multistep disease driven by the activation of specific oncogenic pathways concomitantly with the loss of function of tumor suppressor genes that act as sentinels to control physiological growth. The conservation of most of these signaling pathways in Drosophila , and the ability to easily manipulate them genetically, has made the fruit fly a useful model organism to study cancer biology. In this review we outline the basic mechanisms and signaling pathways conserved between humans and flies responsible of inducing uncontrolled growth and cancer development. Second, we describe classic and novel Drosophila models used to study different cancers, with the objective to discuss their strengths and limitations on their use to identify signals driving growth cell autonomously and within organs, drug discovery and for therapeutic approaches.

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Chromosomal Instability Induces Cellular Invasion in Epithelial Tissues

Cited by 31 publications

References 68 publications

Two-Faced: Roles of JNK Signalling During Tumourigenesis in the Drosophila Model

Two-Faced: Roles of JNK Signalling During Tumourigenesis in the Drosophila Model

Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance

Drosophila melanogaster: A Model Organism to Study Cancer

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