Rab5 activation as a tumor cell migration switch

Mendoza, Pablo; Díaz, Jorge; Silva, Patricio; Torres, Vicente A.

doi:10.4161/sgtp.28195

Cited by 22 publications

(21 citation statements)

References 22 publications

(29 reference statements)

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“…and detachment at the rear of the cell [18,19]. Accumulating evidence has suggested a link between cell migration and small GTPases [20][21][22][23][24]. Then, we next tested whether Rap2B is involved in cell migration by using a wound-healing assay.…”

Section: R E T R a C T E Dmentioning

confidence: 99%

Retraction: ‘p53‐induced Rap2B positively regulates migration in cells exposed to glucose deprivation’ by D.‐S. Pei, J.‐H. Di, W.‐Q. Du and J.‐N. Zheng

Pei

et al. 2015

Molecular Carcinogenesis

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The above article, published online on July 2, 2015 in Wiley Online Library (http://wileyonlinelibrary.com), has been retracted by agreement between the authors; the journal Editor‐in‐Chief, John DiGiovanni; and Wiley Periodicals, Inc. The retraction has been agreed because author Dong‐Sheng Pei submitted the paper to the journal without permission from his co‐authors. © 2015 Wiley Periodicals, Inc. REFERENCE Pei, D.‐S., Di, J.‐H., Du, W.‐Q. and Zheng, J.‐N. (2015), p53‐induced Rap2B positively regulates migration in cells exposed to glucose deprivation. Mol. Carcinog. doi:

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Section: R E T R a C T E Dmentioning

confidence: 99%

Retraction: ‘p53‐induced Rap2B positively regulates migration in cells exposed to glucose deprivation’ by D.‐S. Pei, J.‐H. Di, W.‐Q. Du and J.‐N. Zheng

Pei

et al. 2015

Molecular Carcinogenesis

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“…As a model system, we study doxycycline-inducible, RAB5A-expressing populations of human mammary epithelial MCF-10A cells. RAB5A is a master regulator of the endocytic activity of the cell and it plays an important role in the dissemination of aggressive breast tumours [38,39,40]. In control monolayers, cell density increases due to mitotic division, which causes a near complete kinetic arrest akin to a jamming or rigidity transition [32,41].…”

Section: Introductionmentioning

confidence: 99%

Giant fluctuations and structural effects in a flocking epithelium

Giavazzi¹,

Malinverno²,

Corallino³

et al. 2017

J. Phys. D: Appl. Phys.

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Abstract. Epithelial cells cultured in a monolayer are very motile in isolation but reach a near-jammed state when mitotic division increases their number above a critical threshold. We have recently shown that a monolayer can be reawakened by over-expression of a single protein, RAB5A, a master regulator of endocytosis. This reawakening of motility was explained in term of a flocking transition that promotes the emergence of a large-scale collective migratory pattern. Here we focus on the impact of this reawakening on the structural properties of the monolayer. We find that the unjammed monolayer is characterised by a fluidisation at the single cell level and by enhanced non-equilibrium large-scale number fluctuations at a larger length scale. Also with the help of numerical simulations, we trace back the origin of these fluctuations to the selfpropelled active nature of the constituents and to the existence of a local alignment mechanism, leading to the spontaneous breaking of the orientational symmetry.

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“…Through endocytosis, internalized molecules are first transported into early endosomes and often further targeted into late endosomes and lysosomes, leading to degradation of the cargo molecules. This endocytic event is involved in various cellular processes, such as cell motility, cell proliferation, and oncogenesis (8)(9)(10)(11). Previous studies in Drosophila have demonstrated that endocytosis also plays a crucial role in cell competition where cells with different properties compete with each other for survival (12)(13)(14).…”

mentioning

confidence: 99%

Rab5-regulated endocytosis plays a crucial role in apical extrusion of transformed cells

Saitoh

Maruyama

Yako

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Newly emerging transformed cells are often eliminated from epithelial tissues. Recent studies have revealed that this cancer-preventive process involves the interaction with the surrounding normal epithelial cells; however, the molecular mechanisms underlying this phenomenon remain largely unknown. In this study, using mammalian cell culture and zebrafish embryo systems, we have elucidated the functional involvement of endocytosis in the elimination of RasV12-transformed cells. First, we show that Rab5, a crucial regulator of endocytosis, is accumulated in RasV12-transformed cells that are surrounded by normal epithelial cells, which is accompanied by upregulation of clathrin-dependent endocytosis. Addition of chlorpromazine or coexpression of a dominant-negative mutant of Rab5 suppresses apical extrusion of RasV12 cells from the epithelium. We also show in zebrafish embryos that Rab5 plays an important role in the elimination of transformed cells from the enveloping layer epithelium. In addition, Rab5-mediated endocytosis of E-cadherin is enhanced at the boundary between normal and RasV12 cells. Rab5 functions upstream of epithelial protein lost in neoplasm (EPLIN), which plays a positive role in apical extrusion of RasV12 cells by regulating protein kinase A. Furthermore, we have revealed that epithelial defense against cancer (EDAC) from normal epithelial cells substantially impacts on Rab5 accumulation in the neighboring transformed cells. This report demonstrates that Rab5-mediated endocytosis is a crucial regulator for the competitive interaction between normal and transformed epithelial cells in mammals.cell competition | endocytosis | apical extrusion | Rab5 | RasV12

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Rab5 activation as a tumor cell migration switch

Cited by 22 publications

References 22 publications

Retraction: ‘p53‐induced Rap2B positively regulates migration in cells exposed to glucose deprivation’ by D.‐S. Pei, J.‐H. Di, W.‐Q. Du and J.‐N. Zheng

Retraction: ‘p53‐induced Rap2B positively regulates migration in cells exposed to glucose deprivation’ by D.‐S. Pei, J.‐H. Di, W.‐Q. Du and J.‐N. Zheng

Giant fluctuations and structural effects in a flocking epithelium

Rab5-regulated endocytosis plays a crucial role in apical extrusion of transformed cells

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