Snail regulates p21WAF/CIP1 expression in cooperation with E2A and Twist

Takahashi, Eishi; Funato, Noriko; Higashihori, Norihisa; Hata, Yuiro; Gridley, Thomas; Nakamura, Masataka

doi:10.1016/j.bbrc.2004.10.148

Cited by 41 publications

(34 citation statements)

References 31 publications

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“…Several transcriptional repressors of the CDH1 gene have been indentified. They include the basic helix-loop-helix (bHLH) family members twist and the E2A gene product E12/47, members of the snail family, snail1 and snail2, and members of the zinc finger homeobox (ZFH) family of repressors, ZEB1 and ZEB2 [3][4][5][6][7][8][9][10][11][12][13][14]. The purpose of this review is to summarize the knowledge about the molecular interconnections of E-cadherin, β-catenin, and WNT signaling to these transcriptional repressors, in particular to ZEB1.…”

Section: Introductionmentioning

confidence: 99%

E-cadherin, β-catenin, and ZEB1 in malignant progression of cancer

Schmalhofer

Brabletz

2009

Cancer Metastasis Rev

698

595

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The embryonic program 'epithelial-mesenchymal transition' (EMT) is activated during tumor invasion in disseminating cancer cells. Characteristic to these cells is a loss of E-cadherin expression, which can be mediated by EMT-inducing transcriptional repressors, e.g. ZEB1. Consequences of a loss of E-cadherin are an impairment of cell-cell adhesion, which allows detachment of cells, and nuclear localization of beta-catenin. In addition to an accumulation of cancer stem cells, nuclear beta-catenin induces a gene expression pattern favoring tumor invasion, and mounting evidence indicates multiple reciprocal interactions of E-cadherin and beta-catenin with EMT-inducing transcriptional repressors to stabilize an invasive mesenchymal phenotype of epithelial tumor cells.

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Section: Introductionmentioning

confidence: 99%

E-cadherin, β-catenin, and ZEB1 in malignant progression of cancer

Schmalhofer

Brabletz

2009

Cancer Metastasis Rev

698

595

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“…TGF-␤ has multiple roles including being a potent growth inhibitor of epithelial cells and has been associated with effects on G1 phase cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors [Yue and Mulder, 2001;Takahashi et al, 2004;Vega et al, 2004;Pardali et al, 2005]. Using Smad and non-Smad pathways, TGF-␤ signaling through ALK5/T ␤ RI could induce a growth inhibitory response via p21/p15 [Matsuyama et al, 2003].…”

Section: Complexity Of Tgf-␤ Signalingmentioning

confidence: 99%

Complexity in Interpretation of Embryonic Epithelial-Mesenchymal Transition in Response to Transforming Growth Factor-β Signaling

Ahmed

Nawshad

2007

Cells Tissues Organs

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Epithelial-mesenchymal transition (EMT) is a highly conserved and fundamental process that governs morphogenesis in development and may also contribute to cancer metastasis. Transforming growth factor (TGF-β) is a potent inducer of EMT in various developmental and tumor systems. The analysis of TGF-β signal transduction pathways is now considered a critically important area of biology, since many defects occur in these pathways in embryonic development. The complexity of TGF-β signal transduction networks is overwhelming due to the large numbers of interacting constituents, complicated feedforward, feedback and crosstalk circuitry mechanisms that they involve in addition to the cellular kinetics and enzymatics that contribute to cell signaling. As a result of this complexity, apparently simple but highly important questions remain unanswered, that is, how do epithelial cells respond to such TGF-β signals? System biology and cellular kinetics play a crucial role in cellular function; omissions of such a critical contributor may lead to inaccurate understanding of embryonic EMT. In this review, we identify and explain why certain conditions need to be considered for a true representation of TGF-β signaling in vivo to better understand the controlled, yet delicate mechanism of embryonic EMT.

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“…Drug-induced downregulation of Snail was connected with upregulation of p21 and G1 phase arrest (46). However, those who first found the repression effect of Snail on p21 (47), already indicate it may be dependend on the type of the cell line. In an epithelial cell line (MDCK cells), Snail induced G0/G1 arrest through increased expression of p21.…”

Section: Discussionmentioning

confidence: 99%

SNAILs promote G1 phase in selected cancer cells

Xue

Zhou

et al. 2015

Int J Oncol

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Abstract. Cells can acquire a stem-like cell phenotype through epithelial-mesenchymal transition (EMT). However, it is not known which of the stem-like cancer cells are generated by these phenotype transitions. We studied the EMT-inducing roles of SNAILs (the key inducers for the onset of EMT) in selected cancer cells (lung cancer cell line with relatively stable genome), in order to provide more implications for the investigation of EMT-related phenotype transitions in cancer. However, SNAILs fail to induce completed EMT. In addition, we proved that Snail accelerates the early G1 phase whereas Slug accelerates the late G1 phase. Blocking G1 phase is one of the basic conditions for the onset of EMT-related phenotype transitions (e.g., metastasis, acquring stemness). The discovery of this unexpected phenomenon (promoting G1 phase) typically reveals the heterogeneity of cancer cells. The onset of EMT-related phenotype transitions in cancer needs not only the induction and activation of SNAILs, but also some particular heredity alterations (genetic or epigenetic alterations, which cause heterogeneity). The new connection between heredity alteration (heterogeneity) and phenotype transition suggests a novel treatment strategy, the heredity alteration-directed specific target therapy. Further investigations need to be conducted to study the relevant heredity alterations. IntroductionCancer stem cell (CSC) is a cell within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor (1). Although it has been proven that epithelial-mesenchymal transition (EMT) can generate cells with stem cell properties (2), it is still unknown which of the stem-like cancer cells are generated by these phenotype transitions.The function of Snail genes is best known for induction of EMT. Both in development and during carcinoma progression, Snail1 (Snail) is expressed at the onset of the transition, whereas Snail2 (Slug), Zeb genes, E47 and Twist are subsequently induced to maintain the migratory mesenchymal state (3). As transcriptional repressors, Snail and Slug can regulate the expression of genes mediating therapeutic resistance and acquiring of stem-like phenotype in ovarian cancer cells (4).Snail and Slug have complicated interactions with many key molecules. Snail can cause functional deficiency of p53 in tumor cells with mutant KRAS (5). We know GSK3β, the downstream molecule of Akt (6), can phosphorylate Snail to cause the degradation or the nuclear export of Snail (7). However, KRAS can interact with the PI3K/Akt pathway (8), and then affect GSK3β. Slug can escape degradation when p53 is mutant in lung cancer (9). In addition, the experssion of Slug can be regulated by mutant KRAS in colon cancer cells (10). Snail and Slug are also connected to other key molecules (e.g., EGFR, ERCC1) (11-13).Certain key molecules, including KRAS, p53, EGFR, ERCC1, are all connected to EMT (11,[14][15][16] and stem cell biology (17)(18)(19)(20). This makes the SNAIL-related ph...

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Snail regulates p21WAF/CIP1 expression in cooperation with E2A and Twist

Cited by 41 publications

References 31 publications

E-cadherin, β-catenin, and ZEB1 in malignant progression of cancer

E-cadherin, β-catenin, and ZEB1 in malignant progression of cancer

Complexity in Interpretation of Embryonic Epithelial-Mesenchymal Transition in Response to Transforming Growth Factor-β Signaling

SNAILs promote G1 phase in selected cancer cells

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