The Snail Family in Normal and Malignant Haematopoiesis

Carmichael, Catherine; Haigh, Jody J.

doi:10.1159/000448655

Cited by 11 publications

(5 citation statements)

References 157 publications

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“…Interestingly, EMT transcription factors of the SNAI family are also expressed during hematopoiesis 114 and evidence is accumulating that they are also involved in malignant transformation toward leukemia. 115 Further research will be necessary to determine whether they use similar converging/complementary pathways in the context of leukemia, as was previously observed during carcinoma progression.…”

Section: Zeb Downstream Signaling In Epithelial and Hematopoietic Cellsmentioning

confidence: 99%

ZEB Proteins in Leukemia: Friends, Foes, or Friendly Foes?

et al. 2018

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ZEB1 and ZEB2 play pivotal roles in solid cancer metastasis by allowing cancer cells to invade and disseminate through the transcriptional regulation of epithelial-to-mesenchymal transition. ZEB expression is also associated with the acquisition of cancer stem cell properties and therapy resistance. Consequently, expression levels of ZEB1/2 and of their direct target genes are widely seen as reliable prognostic markers for solid tumor aggressiveness and cancer patient outcome.Recent loss-of-function mouse models demonstrated that both ZEBs are also essential hematopoietic transcription factors governing blood lineage commitment and fidelity. Interestingly, both gain- and loss-of-function mutations have been reported in multiple hematological malignancies. Combined with emerging functional studies, these data suggest that ZEB1 and ZEB2 can act as tumor suppressors and/or oncogenes in blood borne malignancies, depending on the cellular context. Here, we review these novel insights and discuss how balanced expression of ZEB proteins may be essential to safeguard the functionality of the immune system and prevent leukemia.

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Section: Zeb Downstream Signaling In Epithelial and Hematopoietic Cellsmentioning

confidence: 99%

ZEB Proteins in Leukemia: Friends, Foes, or Friendly Foes?

et al. 2018

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“…These observations are contrasted by evidence that experimental induction of enforced or stable mesenchymal features abrogate metastatic outgrowth in preclinical models, and that metastases display similar or enhanced epithelial properties relative to their primary tumours [22][23][24][25] . Although much of the work on EMP in cancer focuses on carcinomas specifically, related plasticity programmes are described in other cancer types, including sarcomas 26 and haematogenous tumours 27 . Changes in transcriptional programmes that are consistent with EMP have also been identified in stromal cells, likely contributing to the pathobiology of the tumour microenvironment [28][29][30] .…”

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confidence: 99%

Controversies around epithelial–mesenchymal plasticity in cancer metastasis

et al. 2019

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Experimental evidence accumulated over decades has implicated epithelial-mesenchymal plasticity (EMP), which collectively encompasses epithelial-mesenchymal transition and the reverse process of mesenchymal-epithelial transition, in tumour metastasis, cancer stem cell generation and maintenance, and therapeutic resistance. However, the dynamic nature of EMP processes, the apparent need to reverse mesenchymal changes for the development of macrometastases and the likelihood that only minor cancer cell subpopulations exhibit EMP at any one time have made such evidence difficult to accrue in the clinical setting. In this Perspectives article, we outline the existing preclinical and clinical evidence for EMP and reflect on recent controversies, including the failure of initial lineage-tracing experiments to confirm a major role for EMP in dissemination, and discuss accumulating data suggesting that epithelial features and/or a hybrid epithelial-mesenchymal phenotype are important in metastasis. We also highlight strategies to address the complexities of therapeutically targeting the EMP process that give consideration to its spatially and temporally divergent roles in metastasis, with the view that this will yield a potent and broad class of therapeutic agents.Epithelial-mesenchymal transition (EMT) has well established roles in developmental programmes involved in generating new tissues and organs, and is followed, in most cases, *

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“…The Snail1 protein has an amino-terminal basic amino acid-rich domain and a carboxyl-terminal DNA-binding domain, and these two special domains regulate its interaction with co-repressors and the epigenetic remodeling complex and DNA binding, respectively. A serine rich domain (SRD) and nuclear export sequence (NSE) control the stability and subcellular location of the Snail1 protein (21). As a transcription factor, snail1 functions through binding to the E-box element of the 5'-CANNTG-3' core base sequence in the promoter region of many tumor-related genes (22).…”

Section: Discussionmentioning

confidence: 99%

Mechanisms underlying the increased chemosensitivity of bortezomib-resistant multiple myeloma by silencing nuclear transcription factor Snail1

Huang

Liang

et al. 2018

Oncol Rep

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The Snail family transcriptional repressor 1 gene (Snail1) was screened in multiple myeloma cells (MMCs) from bortezomib-resistant MM patients and was found to be significantly associated with the development of drugresistance mechanisms. In the present study, we first confirmed that the protein expression of Snail1 in bortezomib-resistant MMCs was significantly higher than that in MMCs without bortezomib resistance. The mechanistic studies confirmed that the enhancement of Snail1 expression in bortezomib-resistant MMCs directly upregulated transcription of the intracellular MDR1 gene to immediately develop multiple drug resistance mechanisms and inhibited P53 protein expression through the Snail1/hsa-miRNA-22-3p/P53 pathway to inhibit tumor cell apoptosis. By upregulating MDR1 and downregulating P53, Snail1 induced the drug resistance of MMCs to bortezomib, while Snail1 gene silencing effectively improved the drug sensitivity of MMCs to bortezomib chemotherapy. The present study further elucidated the drug resistance mechanisms of MMCs and provides evidence for increased clinical efficacy of bortezomib in MM patients.

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The Snail Family in Normal and Malignant Haematopoiesis

Cited by 11 publications

References 157 publications

ZEB Proteins in Leukemia: Friends, Foes, or Friendly Foes?

ZEB Proteins in Leukemia: Friends, Foes, or Friendly Foes?

Controversies around epithelial–mesenchymal plasticity in cancer metastasis

Mechanisms underlying the increased chemosensitivity of bortezomib-resistant multiple myeloma by silencing nuclear transcription factor Snail1

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