Upregulation of myosin Va by Snail is involved in cancer cell migration and metastasis

Lan, Linxiang; Han, Han; Zuo, Hui-Jing; Chen, Zhi Guo; Du, Yantao; Zhao, Wei; Gu, Jin; Zhang, Zhiqian

doi:10.1002/ijc.24641

Cited by 77 publications

(80 citation statements)

References 38 publications

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“…Electrophoretic mobility shift assay (EMSA) was performed using the LightShift chemilluminescent EMSA kit (Pierce, Rockford, IL) essentially the same as described 63 . The double-stranded oligonucleotide used as a probe for EMSA corresponds to the following sequence in the putative PBX3 WT binding site of the CACNA2D1 promoter region, 5 0 -TCCTCCCTGAT TTATTCCCCCG-3 0 .…”

Section: Discussionmentioning

confidence: 99%

PBX3 is targeted by multiple miRNAs and is essential for liver tumour-initiating cells

Han

Zhao

et al. 2015

Nat Commun

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Tumour-initiating cells (TICs) are advocated to constitute the sustaining force to maintain and renew fully established malignancy; however, the molecular mechanisms responsible for these properties are elusive. We previously demonstrated that voltage-gated calcium channel a2d1 subunit marks hepatocellular carcinoma (HCC) TICs. Here we confirm directly that a2d1 is a HCC TIC surface marker, and identify let-7c, miR-200b, miR-222 and miR-424 as suppressors of a2d1 þ HCC TICs. Interestingly, all the four miRNAs synergistically target PBX3, which is sufficient and necessary for the acquisition and maintenance of TIC properties. Moreover, PBX3 drives an essential transcriptional programme, activating the expression of genes critical for HCC TIC stemness including CACNA2D1, EpCAM, SOX2 and NOTCH3. In addition, the expression of CACNA2D1 and PBX3 mRNA is predictive of poor prognosis for HCC patients. Collectively, our study identifies an essential signalling pathway that controls the switch of HCC TIC phenotypes.

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Section: Discussionmentioning

confidence: 99%

PBX3 is targeted by multiple miRNAs and is essential for liver tumour-initiating cells

Han

Zhao

et al. 2015

Nat Commun

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“…Snail is known to act as a transcriptional repressor; very few reports, however, have shown that Snail activates target genes, with the exception of the direct activation of myosin Va by Snail (35). Here, we showed that the SNAG domain of Snail is responsible for the promotion of ERCC1 transcription.…”

Section: Discussionmentioning

confidence: 53%

Regulation of Excision Repair Cross-Complementation Group 1 by Snail Contributes to Cisplatin Resistance in Head and Neck Cancer

Hsu

Lan

Huang

et al. 2010

Clinical Cancer Research

134

108

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Purpose: We investigated the mechanism and clinical significance of the epithelial-mesenchymal transition (EMT)-induced chemoresistance in head and neck squamous cell carcinoma (HNSCC).Experimental Design: The correlation between the expression of different EMT regulators and chemoresistance genes, such as excision repair cross complementation group 1 (ERCC1), was evaluated in cancer cell lines from the NCI-60 database and four human HNSCC cell lines. Ectopic expression of Snail or short-interference RNA-mediated repression of Snail or ERCC1 was done in HNSCC cell lines. Cell viability was examined for cells after cisplatin treatment. A luciferase reporter assay and chromatin immunoprecipitation were used to identify the transcriptional regulation of ERCC1 by Snail. Immunohistochemical analysis of Snail, Twist1, ERCC1, hypoxia inducible factor-1 α (HIF-1α), and NBS1 were done in samples from 72 HNSCC patients receiving cisplatin-based chemotherapy.Results: The correlation between the expression of Snail and ERCC1 was confirmed in different cell lines, including HNSCC cells. In HNSCC cell lines, overexpression of Snail in the low endogenous Snail/ ERCC1 cell lines FaDu or CAL-27 increased ERCC1 expression, and hypoxia or overexpression of NBS1 also upregulated ERCC1. Knockdown of Snail in the high endogenous Snail/ERCC1 cell line OECM-1 downregulated ERCC1 expression and attenuated cisplatin resistance. Furthermore, suppression of ERCC1 in Snail-or NBS1-overexpressing HNSCC cells enhanced sensitivity to cisplatin. Snail directly regulated ERCC1 transcription. In patients with HNSCC, coexpression of Snail and ERCC1 correlated with cisplatin resistance and a poor prognosis.Conclusions: Activation of ERCC1 by Snail is critical in the generation of cisplatin resistance of HNSCC cells. Clin Cancer Res; 16(18); 4561-71. ©2010 AACR.The epithelial-mesenchymal transition (EMT), a major mechanism of cancer metastasis, is initiated by repression of the epithelial adhesion molecule E-cadherin by several transcription factors, including Snail (also known as Snail1), Slug (also known as Snail2), Twist1, Zeb1, SIP1, and E47 (1). In most human cancers, metastatic tumors are resistant to chemotherapy; therefore, patients with such tumors typically have poor outcomes. Emerging evidence suggests a correlation between EMT and the resistance to chemotherapy of cancer cells. For example, colorectal cancer cells that are resistant to oxaliplatin undergo phenotypic changes indicative of an EMT (2). Direct regulation of Akt2 by Twist contributes to paclitaxel resistance in breast cancer cells (3). Induction of EMT in breast cancer cells leads to an enrichment of cells with stem-like properties and chemoresistance (4). A recent report found that Zeb1 and other EMT regulators allow pancreatic cancer cells to maintain drug resistance (5). Taken together, these studies suggest that diverse types of cancer cells acquire drug-resistant phenotypes during EMT. Although there is an evident association among EMT, metastasis, and chemoresis...

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“…Multiple functions have been assigned to this actin-dependent molecular motor, including the transport of melanosomes, smooth endoplasmic reticulum, recycling endosomes, neurotransmitter vesicles, mRNA (Reck-Peterson et al 2000, Langford 2002, Salerno et al 2008, and neuroendocrine vesicles (Rudolf et al 2003). A role for MYO5A in tumor cell migration, invasion, and metastasis has recently been described (Du et al 2007, Lan et al 2010. Thus, our finding that MYO5A gene and protein expression is Endocrine-Related Cancer (2010) 17 361-371…”

Section: Discussionmentioning

confidence: 70%

Differential gene expression profiles of invasive and non-invasive non-functioning pituitary adenomas based on microarray analysis

Galland¹,

Lacroix²,

Saulnier³

et al. 2010

Endocrine-Related Cancer

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Non-functioning pituitary adenomas (NFPAs) may be locally invasive. Markers of invasiveness are needed to guide patient management and particularly the use of adjuvant radiotherapy. To examine whether invasive NFPAs display a specific gene expression profile relative to non-invasive tumors, we selected 40 NFPAs (38 of the gonadotroph type) and classified them as invasive (nZ22) or non-invasive (nZ18) on the basis of magnetic resonance imaging and surgical findings. We then performed pangenomic analysis with the 44k Agilent human whole genome expression oligonucleotide microarray in order to identify genes with differential expression between invasive and non-invasive NFPAs. Candidate genes were then tested in qRT-PCR. Prediction class analysis showed that the expression of 346 genes differed between invasive and non-invasive NFPAs (P!0.001), of which 233 genes were up-regulated and 113 genes were down-regulated in invasive tumors. On the basis of Ingenuity networks and the degree of up-or down-regulation in invasive versus non-invasive tumors, 35 genes were selected for expression quantification by qRT-PCR. Overexpression of only four genes was confirmed, namely IGFBP5 (PZ0.02), MYO5A (PZ0.04), FLT3 (PZ0.01), and NFE2L1 (PZ0.02). At the protein level, only myosin 5A (MYO5A) immunostaining was stronger in invasive than in non-invasive NFPAs. Molecular signature allows to differentiate 'grossly' invasive from non-invasive NFPAs. The product of one of these genes, MYO5A, may be a useful marker of tumor invasiveness.

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Upregulation of myosin Va by Snail is involved in cancer cell migration and metastasis

Cited by 77 publications

References 38 publications

PBX3 is targeted by multiple miRNAs and is essential for liver tumour-initiating cells

PBX3 is targeted by multiple miRNAs and is essential for liver tumour-initiating cells

Regulation of Excision Repair Cross-Complementation Group 1 by Snail Contributes to Cisplatin Resistance in Head and Neck Cancer

Differential gene expression profiles of invasive and non-invasive non-functioning pituitary adenomas based on microarray analysis

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