Snail blocks the cell cycle and confers resistance to cell death.

By Sonia Vega, A. V. Morales, Oscar H. Ocaña, Francisco Valdés, I. Fabregat, M. Nieto. Genes & Development, 2004

869 citations recorded by the source corpus.

The Snail zinc-finger transcription factors trigger epithelial-mesenchymal transitions (EMTs), endowing epithelial cells with migratory and invasive properties during both embryonic development and tumor progression. During EMT, Snail provokes the loss of epithelial markers, as well as changes in cell shape and the expression of mesenchymal markers. Here, we show that in addition to inducing dramatic phenotypic alterations, Snail attenuates the cell cycle and confers resistance to cell death induced by the withdrawal of survival factors and by pro-apoptotic signals. Hence, Snail favors changes in cell shape versus cell division, indicating that with respect to oncogenesis, although a deregulation/increase in proliferation is crucial for tumor formation and growth, this may not be so for tumor malignization. Finally, the resistance to cell death conferred by Snail provides a selective advantage to embryonic cells to migrate and colonize distant territories, and to malignant cells to separate from the primary tumor, invade, and form metastasis.

Subfields: Cell Biology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/4734abd50e49ab11fd8e2ec938b4905d564cd041

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cell Biology

1. M. Nieto
2. R. Weinberg
3. E. Hay
4. Raghu Kalluri
5. Jing Yang
6. A. Cano
7. F. Portillo
8. G. Moreno-Bueno

In Molecular Biology

1. R. Weinberg
2. M. Nieto
3. Thomas Brabletz
4. J. P. Thiery
5. Jing Yang
6. Raghu Kalluri
7. Simone Brabletz
8. E. Hay

In Oncology

1. R. Weinberg
2. M. Nieto
3. Thomas Brabletz
4. Jing Yang
5. J. P. Thiery
6. Raghu Kalluri
7. E. Hay
8. Simone Brabletz

Citations in the corpus

• Systems Biology of Cancer Metastasis (2019, background): “For example, while cells in the initial tumor mass may be proliferative, many reports indicate that disseminating cells or cells undergoing an epithelial-to-mesenchymal transition (EMT) largely suspend proliferation (Rojas-Puentes et al., 2016; Vega et al., 2004; Zheng et al., 2015).”
• The ins and outs of the epithelial to mesenchymal transition in health and disease. (2011, background): “Furthermore, women with mutations in the BRCA1 gene show a predisposition to developing breast tumors of the basal type, which has been linked to genetic alterations present before neoplastic transformation and to the activation of the EMT inducer Snail2 (Slug) that preferentially directs the progen”
• Migrating cancer stem cells — an integrated concept of malignant tumour progression (2005, background): “Recent publications describe the potential of EMT-associated transcriptional repressors, such as SLUG, to induce growth arrest and resistance to apoptosis induced by chemotherap”
• Epithelial-Mesenchymal Transition in Cancer: A Historical Overview (2020, background): “Snail, one of EMT transcription factors, could dramatically impair cell-cycle progression by repressing the transcription of cyclin D2 whose activity was required for cell division [90].”
• Epithelial Plasticity: A Common Theme in Embryonic and Cancer Cells (2013, background): “mented to promote their arrival to their destination (78).”
• Epithelial-mesenchymal plasticity in cancer progression and metastasis (2019, background): “A) Genetic deletion of EMT-TFs Snai1 and Twist1 does not reduce metastasis in KPC model of mouse pancreatic cancer.”
• A gene regulatory network orchestrates neural crest formation (2008, background): “Upon delamination, Snail expression decreases, which allows the cyclin levels to rise and the cell cycle to progres”
• Transcriptional regulation of cell polarity in EMT and cancer (2008, background): “The mechanisms underlying the upregulation of mesenchymal motility or survival genes are still poorly understood, but they probably involve indirect activation pathways (Vega et al., 2004; Jordà et al., 2005; Grotegut et al., 2006; Beltran et al., 2008).”
• Depletion of Carcinoma-Associated Fibroblasts and Fibrosis Induces Immunosuppression and Accelerates Pancreas Cancer with Diminished Survival (2014, neutral): “This could be explained by the observation that cancer cells with EMT program likely do not proliferate (Tsai et al., 2012; Vega et al., 2004), further confirming their low-cyclingstem-cell status.”
• Epithelial-mesenchymal transitions: twist in development and metastasis. (2004, neutral): “2002) but attenuates proliferation, rather than promoting Vega, S., Morales, A.V., Ocana, O.H., Valdes, F., Fabregat, I., and growth (Vega et al., 2004).”
• The basics of epithelial–mesenchymal transition (EMT): A study from a structure, dynamics, and functional perspective (2019, background): “transcriptional repression of genes engaged in several features of programmed cell death (Vega et al., 2004).”
• The mesenchymal cell, its role in the embryo, and the remarkable signaling mechanisms that create it (2005, background): “, 2004), which promotes cell survival, as well as EMT (Vega et al., 2004).”
• Epithelial to Mesenchymal Transition induces cell cycle arrest and parenchymal damage in renal fibrosis (2015, positive): “Over–expression of Snai1 in cultured canine kidney epithelial cells (MDCK) induced a cell cycle arrest involving enhanced p21 WAF1/CIP1 expression 47 .”
• EMT and tumor metastasis (2015, background): “When the cancer cells are going through this differentiation, a reduction in their cell cycle progression is expected [27].”