C-kit induces epithelial-mesenchymal transition and contributes to salivary adenoid cystic cancer progression

Tang, Yaling; Fan, Yunlong; Jiang, Jian; Li, Kaide; Zheng, Min; Chen, Wei; Ma, Xiangrui; Geng, Ning; Chen, Qianming; Chen, Yu; Liang, Xin‐hua

doi:10.18632/oncotarget.1606

Cited by 37 publications

(22 citation statements)

References 45 publications

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“…Beside the observations of increased c-kit expression in epicardial EMT induced in vivo and in vitro by TGF-beta, there is mounting evidence that similar c-kit expression occurs in extra-cardiac tissues undergoing EMT as well as in EMT leading to tumorigenesis 99, 100 . Studies of in vitro TGF-beta induced EMT in non-cardiac epithelial cell lines have shown an increase in expression of c-kit and mesenchymal markers, essentially mirroring the results obtained with induction of EMT in human epicardial mesothelium 66 .…”

Section: Introductionmentioning

confidence: 99%

“String Theory” of c-kit ^pos Cardiac Cells

Keith

Bolli

2015

Circulation Research

111

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Although numerous preclinical investigations have consistently demonstrated salubrious effects of c-kitpos cardiac cells administered after myocardial infarction, the mechanism of action remains highly controversial. We and others have found little or no evidence that these cells differentiate into mature functional cardiomyocytes, suggesting paracrine effects. In this review, we propose a new paradigm predicated on a comprehensive analysis of the literature, including studies of cardiac development; we have dubbed this conceptual construct “string theory of c-kitpos cardiac cells” because it reconciles multifarious and sometimes apparently discrepant results. There is strong evidence that, during development, the c-kit receptor is expressed in different pools of cardiac progenitors (some capable of robust cardiomyogenesis and others with little or no contribution to myocytes). Accordingly, c-kit positivity, in itself, does not define the embryonic origins, lineage capabilities, or differentiation capacities of specific cardiac progenitors. C-kitpos cells derived from the first heart field (FHF) exhibit cardiomyogenic potential during development, but these cells are likely depleted shortly before or after birth. The residual c-kitpos cells found in the adult heart are probably of proepicardial origin, possess a mesenchymal phenotype, and are capable of contributing significantly only to non-myocytic lineages (fibroblasts, smooth muscle cells, endothelial cells). If these two populations (FHF and proepicardium) express different levels of c-kit, the cardiomyogenic potential of FHF progenitors might be reconciled with recent results of c-kitpos cell lineage tracing studies. The concept that c-kit expression in the adult heart identifies epicardium-derived, non-cardiomyogenic precursors with a mesenchymal phenotype helps to explain the beneficial effects of c-kitpos cell administration to ischemically damaged hearts despite the observed paucity of cardiomyogenic differentiation of these cells.

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Section: Introductionmentioning

confidence: 99%

“String Theory” of c-kit ^pos Cardiac Cells

Keith

Bolli

2015

Circulation Research

111

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“…However, these studies did not assess the role of GAS6, and MP470 can target different tyrosine kinases that have been already defined as EMT inducers (for instance, c-KIT; ref. 38). Here, we show that AXL activation by GAS6 is necessary to promote strong EMT signaling through the involvement of many EMT transcription factors.…”

Section: Discussionmentioning

confidence: 68%

Therapeutic Activity of Anti-AXL Antibody against Triple-Negative Breast Cancer Patient-Derived Xenografts and Metastasis

Leconet

Chentouf

Manoir

et al. 2017

Clinical Cancer Research

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Purpose: AXL receptor tyrosine kinase has been described as a relevant molecular marker and a key player in invasiveness, especially in triple-negative breast cancer (TNBC).Experimental Design: We evaluate the antitumor efficacy of the anti-AXL monoclonal antibody 20G7-D9 in several TNBC cell xenografts or patient-derived xenograft (PDX) models and decipher the underlying mechanisms. In a dataset of 254 basal-like breast cancer samples, genes correlated with AXL expression are enriched in EMT, migration, and invasion signaling pathways.Results: Treatment with 20G7-D9 inhibited tumor growth and bone metastasis formation in AXL-positive TNBC cell xenografts or PDX, but not in AXL-negative PDX, highlighting AXL role in cancer growth and invasion. In vitro stimulation of AXL-positive cancer cells by its ligand GAS6 induced the expression of several EMT-associated genes (SNAIL, SLUG, and VIM) through an intracellular signaling implicating the transcription factor FRA-1, important in cell invasion and plasticity, and increased their migration/invasion capacity. 20G7-D9 induced AXL degradation and inhibited all AXL/GAS6-dependent cell signaling implicated in EMT and in cell migration/invasion.Conclusions: The anti-AXL antibody 20G7-D9 represents a promising therapeutic strategy in TNBC with mesenchymal features by inhibiting AXL-dependent EMT, tumor growth, and metastasis formation.

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“…CD133 or CD44 has been known to be valued as an important CSC or CSC‐like marker in human SACC . This study has found that ectopic expression of HSP27 in SACC cells added the CD133+/CD44+ subpopulation and increased the mammosphere forming ability, a property of the stem cells.…”

Section: Discussionmentioning

confidence: 81%

HSP27 associates with epithelial–mesenchymal transition, stemness and radioresistance of salivary adenoid cystic carcinoma

Chen

Ren

et al. 2018

J Cellular Molecular Medi

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Epithelial–mesenchymal transition (EMT) has been shown to associate with cancer stem cells and radioresistance. However, it is obscure whether EMT itself or specific EMT regulators play causal roles in these properties of salivary adenoid cystic carcinoma (SACC). Here, we exhibited that overexpression of HSP27 drove the migration and invasion, induced EMT, as well as mediated TGF‐β1‐induced EMT in SACC cells, accompanying the up‐regulation of Snail1 and Prrx1. Conversely, HSP27 silencing reduced the migration and invasion and contributed to MET of SACC cells. HSP27 indirectly down‐regulates the expression of E‐cadherin through activating Snail1 and Prrx1 expressions. Overexpression of Snail1 or Prrx1 restored the migration and invasion in HSP27 knockdown cells. Enforced expression of HSP27 enhanced colony formation, CD133+/CD44+ population and radioresistance of SACC cell lines. In addition, HSP27 expression was positively associated with radioresistance and poor prognosis of SACC patients as well as with the expression of Prrx1 or Snail1 in SACC tissues. The data confirm an important function for HSP27 in SACC progression through regulating EMT and stemness, and they imply the possible association between EMT and radioresistance of SACC.

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C-kit induces epithelial-mesenchymal transition and contributes to salivary adenoid cystic cancer progression

Cited by 37 publications

References 45 publications

“String Theory” of c-kit ^pos Cardiac Cells

“String Theory” of c-kit ^pos Cardiac Cells

Therapeutic Activity of Anti-AXL Antibody against Triple-Negative Breast Cancer Patient-Derived Xenografts and Metastasis

HSP27 associates with epithelial–mesenchymal transition, stemness and radioresistance of salivary adenoid cystic carcinoma

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C-kit induces epithelial-mesenchymal transition and contributes to salivary adenoid cystic cancer progression

Cited by 37 publications

References 45 publications

“String Theory” of c-kit pos Cardiac Cells

“String Theory” of c-kit pos Cardiac Cells

Therapeutic Activity of Anti-AXL Antibody against Triple-Negative Breast Cancer Patient-Derived Xenografts and Metastasis

HSP27 associates with epithelial–mesenchymal transition, stemness and radioresistance of salivary adenoid cystic carcinoma

Contact Info

Product

Resources

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“String Theory” of c-kit ^pos Cardiac Cells

“String Theory” of c-kit ^pos Cardiac Cells