Epithelial polarity and proliferation control: links from the <i>Drosophila</i> neoplastic tumor suppressors

Bilder, David

doi:10.1101/gad.1211604

Cited by 512 publications

(512 citation statements)

References 135 publications

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“…In addition, the mutation caused marked mislocalization of Scribble protein away from cell-cell contacts in embryonic keratinocytes (data not shown). Similar mutations in scribble homologues in Drosophila and C. elegans also result in mislocalization of the protein and are suggested to render the protein nonfunctional (Legouis et al, 2000(Legouis et al, , 2003Bilder, 2004). Given these observations we asked whether disruption to Scribble function would affect directed cell migration in vivo.…”

Section: Scribble Is Essential For Wound Healing In Vivomentioning

confidence: 99%

The tumour-suppressor Scribble dictates cell polarity during directed epithelial migration: regulation of Rho GTPase recruitment to the leading edge

Dow

Kauffman

Caddy³

et al. 2006

Oncogene

161

142

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Altered expression of human Scribble is associated with invasive epithelial cancers, however, its role in tumour development remains unclear. Mutations in Drosophila Scribble result in loss of polarity, overproliferation and 3D-tumourous overgrowth of epithelial cells. Using complementation studies in Drosophila we recently demonstrated that expression of human Scribble can also regulate polarity and restrict tissue overgrowth. Here, we have undertaken a detailed study of human Scribble function in the polarized mammary cell line, MCF10A. We show that although Scribble does not seem to be required for apical-basal polarity or proliferation control in MCF10A cells, Scribble is essential for the control of polarity associated with directed epithelial cell migration. Scribble-depleted MCF10A cells show defective in vitro wound closure and chemotactic movement. The cells at the wound edge fail to polarize, show reduced lamellipodia formation and impaired recruitment of Cdc42 and Rac1 to the leading edge. Furthermore, we show that this function is relevant in vivo as Scribble mutant mice show defective epidermal wound healing. This data identifies an essential role for mammalian Scribble in the regulation of the polarity specifically involved in directed epithelial migration.

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Section: Scribble Is Essential For Wound Healing In Vivomentioning

confidence: 99%

The tumour-suppressor Scribble dictates cell polarity during directed epithelial migration: regulation of Rho GTPase recruitment to the leading edge

Dow

Kauffman

Caddy³

et al. 2006

Oncogene

161

142

View full text Add to dashboard Cite

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“…In Drosophila, mutations in the neoplastic tumor suppressor genes, lgl, dlg and scrib, disrupt polarity of epithelia and simultaneously induce overproliferation of epithelial cells with malignant characteristics, indicating the function of the fly tumor suppressors in coupling cell polarity and cell proliferation (Humbert et al, 2003;Bilder, 2004;Humbert et al, this issue). Consistent with this idea, decreased expression of Lgl, Dlg or Scrib is observed in a variety of human tumors (Cavatorta et al, 2004;Nakagawa et al, 2004;Schimanski et al, 2005;Kuphal et al, 2006).…”

Section: Loss Of Epithelial Polarity In Cell Transformationmentioning

confidence: 99%

Linking epithelial polarity and carcinogenesis by multitasking Helicobacter pylori virulence factor CagA

Hatakeyama

2008

Oncogene

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“…One of the best characterized examples is neuroblastoma, a tumor originated from neuroblast stem cells. Normally, Drosophila neuroblasts divide asymmetrically, a process which is controlled by genes regulating cell polarity and cell fate 106,107 . Using Drosophila as a model, three recent studies have shown that the loss of polarity and impairment of asymmetric division in stem cells leads to tumorigenesis [108][109][110] .…”

Section: Asymmetric Division Of Stem Cells and Cancermentioning

confidence: 99%

Somatic stem cells and the origin of cancer

2006

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647Most human cancers derive from a single cell targeted by genetic and epigenetic alterations that initiate malignant transformation. Progressively, these early cancer cells give rise to different generations of daughter cells that accumulate additional mutations, acting in concert to drive the full neoplastic phenotype 1,2 . As we have currently deciphered many of the gene pathways disrupted in cancer, our knowledge about the nature of the normal cells susceptible to transformation upon mutation has remained more elusive. Adult stem cells are those that show long-term replicative potential, together with the capacities of self-renewal and multi-lineage differentiation. These stem cell properties are tightly regulated in normal development, yet their alteration may be a critical issue for tumorigenesis. This concept has arisen from the striking degree of similarity noted between somatic stem cells and cancer cells, including the fundamental abilities to self-renew and differentiate. Given these shared attributes, it has been proposed that cancers are caused by transforming mutations occurring in tissue-specific stem cells 3-9 . This hypothesis has been functionally supported by the observation that among all cancer cells within a particular tumor, only a minute cell fraction has the exclusive potential to regenerate the entire tumor cell population 3,10-13 ; these cells with stem-like properties have been termed cancer stem cells. Cancer stem cells can originate from mutation in normal somatic stem cells that deregulate their physiological programs. Alternatively, mutations may target more committed progenitor cells or even mature cells, which become reprogrammed to acquire stem-like functions 14,15 In any case, mutated genes should promote expansion of stem/progenitor cells, thus increasing their predisposition to cancer development by expanding self-renewal and pluripotency over their normal tendency towards relative quiescency and proper differentiation.

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Epithelial polarity and proliferation control: links from the Drosophila neoplastic tumor suppressors

Cited by 512 publications

References 135 publications

The tumour-suppressor Scribble dictates cell polarity during directed epithelial migration: regulation of Rho GTPase recruitment to the leading edge

The tumour-suppressor Scribble dictates cell polarity during directed epithelial migration: regulation of Rho GTPase recruitment to the leading edge

Linking epithelial polarity and carcinogenesis by multitasking Helicobacter pylori virulence factor CagA

Somatic stem cells and the origin of cancer

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