Developmental transcription factor slug is required for effective re‐epithelialization by adult keratinocytes

Savagner, Pierre; Kusewitt, Donna F.; Carver, Ethan A.; Magnino, Fabrice; Choi, Chagsun; Gridley, Thomas; Hudson, Laurie G.

doi:10.1002/jcp.20188

Cited by 225 publications

(217 citation statements)

References 39 publications

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“…Nevertheless, a significant decrease of MMP9 and mesenchymal markers was detected in CarB-shSnai2 xenografts (Figure 5), suggesting that Snai2 can control certain aspects of tumor invasion/differentiation in determined tumor contexts. These observations are also compatible with the differential roles proposed for Snai1 and Snai2 factors in individual vs collective tumor invasion, or distinct anatomic dissemination of breast and ovarian tumors (Elloul et al, 2005(Elloul et al, , 2006Come et al, 2006), and for Snai2 in wound healing migration (Savagner et al, 2005).…”

Section: Discussionsupporting

confidence: 87%

Snai1 and Snai2 collaborate on tumor growth and metastasis properties of mouse skin carcinoma cell lines

et al. 2008

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Snai1 (Snail) and Snai2 (Slug), the two main members of Snail family factors, are important mediators of epithelial-mesenchymal transitions and involved in tumor progression. We recently reported that Snai1 plays a major role in tumor growth, invasion and metastasis, but the contribution of Snai2 to tumorigenesis is not yet well understood. To approach this question we have silenced Snai2 and/or Snai1 by stable RNA interference in two independent mouse skin carcinoma (HaCa4 and CarB) cell lines. We demonstrate that Snai2 knockdown has a milder effect, but collaborates with Snai1 silencing in reduction of tumor growth potential of either carcinoma cell line when injected into nude mice. Importantly, Snai1 or Snai2 silencing dramatically influences the metastatic ability of squamous carcinoma HaCa4 cells, inducing a strong reduction in liver and lung distant metastasis. However, only Snai1 knockdown has an effective action on invasiveness and fully abolishes tumor cell dissemination into the spleen. These results demonstrate that Snai1 and Snai2 collaborate on primary tumor growth and specifically contribute to site-specific metastasis of HaCa4 cells. These data also indicate that Snai1 is the major regulator of local invasion, supporting a hierarchical participation of both factors in the metastatic process.

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Section: Discussionsupporting

confidence: 87%

Snai1 and Snai2 collaborate on tumor growth and metastasis properties of mouse skin carcinoma cell lines

et al. 2008

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“…Interestingly, dissociation of E-cadherin-mediated junctions can lead to autoregulatory induction of Slug and subsequent repression of E-cadherin transcription (Conacci-Sorrell et al, 2003). A role for Slug was also proposed in EMT associated with re-epitelization of cutaneous wounds, while Snail was not involved (Savagner et al, 2005), consistent with differential expression of these genes observed in TGFb-induced EMT in keratinocytes, renal tubular epithelial cells, and mammary epithelial cells (Zavadil et al, 2004).…”

Section: Snail/slugmentioning

confidence: 76%

TGF-β and epithelial-to-mesenchymal transitions

2005

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Remarkable phenotype plasticity of epithelial cells underlies morphogenesis, epithelial repair and tumor invasiveness. Detailed understanding of the contextual cues and molecular mediators that control epithelial plasticity will be required in order to develop viable therapeutic approaches targeting epithelial-to-mesenchymal transition (EMT), an advanced manifestation of epithelial plasticity. Members of the transforming growth factor (TGF-b) family of growth factors can initiate and maintain EMT in a variety of biological systems and pathophysiological context by activating major signaling pathways and transcriptional regulators integrated in extensive signaling networks. Here we will review the distinct physiological contexts of EMT and the underlying molecular signaling networks controlled by TGF-b.

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“…They regulate cell migration, left-right symmetry, stem cell survival, and epithelial-to-mesenchymal transitions (EMT) during metazoan development (Barrallo-Gimeno and Nieto, 2005;Boyer et al, 2000;Nieto, 2002), as well as dedifferentiation and regeneration in the mature adult (Savagner et al, 2005;Zhao et al, 2002). Members of this family, particularly Snail1 and Snail2, function primarily as repressors of gene transcription, regulating a variety of epithelial-specific genes involved in cell adhesion and epithelial cell identity (Bolos et al, 2003;Kajita et al, 2004;Tripathi et al, 2005).…”

Section: Resultsmentioning

confidence: 99%

Snail2, a mediator of epithelial-mesenchymal transitions, expressed in progenitor cells of the developing endocrine pancreas

Rukstalis

Habener

2007

Gene Expression Patterns

111

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The mammalian pancreas develops by the expansion and morphogenesis of the epithelial cells of the foregut endoderm via the sequential activation of transcription factors that direct differentiation into the various pancreatic lineages. Implicit in this growth and differentiation are the temporal and spatial processes of cell migration and three-dimensional organization, which cooperate to form a properly functioning organ. In many organ systems, such as the kidney, heart, and neural crest derivatives, migration and tissue morphogenesis is accomplished by the transient conversion of stationary epithelial cells to migratory mesenchymal-like cells in a process known as epithelial-mesenchymal transition (EMT). We report the identification of the expression of the transcription factor Snail2/ Slug, a known inducer of EMT and cell movement, in both the endocrine and exocrine cells of the developing mouse pancreas. Snail2 is expressed in Neurogenin3-positive endocrine progenitor cells, and expression is maintained during endocrine cell differentiation where it becomes increasingly restricted to the insulin-producing beta cells and somatostatin-producing delta cells. In the adult pancreas, the expression of Snail2 is maintained at low but detectable levels in all beta cells, indicating a latent role for Snail2 in the mature islet. These findings of Snail2 expression during endocrine pancreas development are relevant to the recent evidence demonstrating the involvement of EMT in the expansion of human islet tissue in vitro. EMT-like events appear to be involved in the development of the mammalian pancreas in vivo.

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Developmental transcription factor slug is required for effective re‐epithelialization by adult keratinocytes

Abstract: Taken together, these findings suggest that Slug plays an important role during wound re-epithelialization in adult skin and indicate that Slug controls some aspects of epithleial cell behavior in adult tissues as well as during embryonic development.

Cited by 225 publications

References 39 publications

Snai1 and Snai2 collaborate on tumor growth and metastasis properties of mouse skin carcinoma cell lines

Snai1 and Snai2 collaborate on tumor growth and metastasis properties of mouse skin carcinoma cell lines

TGF-β and epithelial-to-mesenchymal transitions

Snail2, a mediator of epithelial-mesenchymal transitions, expressed in progenitor cells of the developing endocrine pancreas

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