Notch-1-mediated esophageal carcinoma EC-9706 cell invasion and metastasis by inducing epithelial–mesenchymal transition through Snail

Wang, Tao; Xing, Xuan; Pian, Linping; Gao, Peng; Xu, Hong; Zheng, Yan; Zang, Wenqiao

doi:10.1007/s13277-013-1159-3

Cited by 22 publications

(19 citation statements)

References 28 publications

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“…Notch-1 has been implicated in tumor metastasis in a variety of cancer types [ 14 ]. We investigated whether Notch-1 downregulation influenced the migratory capacity of salivary adenoid cystic carcinoma cells.…”

Section: Resultsmentioning

confidence: 99%

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Notch-1 knockdown suppresses proliferation, migration and metastasis of salivary adenoid cystic carcinoma cells

et al. 2015

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BackgroundNotch-1 promotes invasion and metastasis of cancer cells but its role in salivary adenoid cystic carcinoma (SACC) remains unelucidated. Here, we sought to investigate the effect of Notch-1 knockdown on the invasion and metastasis of SACC cells.MethodsStable ACC-M cells whose Notch-1 was silenced by lentiviral vectors were established. Cellular proliferation was evaluated by the MTT assays and clonogenic assays, apoptosis by flow cytometry and the migration of ACC-M cells by Transwell assays. Metastasis was evaluated by examining the number of lung nodules in Balb⁄c nu⁄nu nude mice bearing subcutaneous SACC xenografts.ResultsOur MTT assay revealed that Notch-1 knockdown significantly suppressed the proliferation of ACC-M cells compared with non-infected or scrambled control cells. Clonogenic assays further showed that Notch-1 knockdown significantly suppressed the clonogenic growth of ACC-M cells (p < 0.01 vs. controls). Our flow cytometry demonstrated that Notch-1 knockdown was associated with a significantly higher proportion of late apoptotic and necrotic cells (p < 0.01 vs. controls). Transwell assays revealed that Notch-1 knockdown markedly reduced the migratory capacity of ACC-M cells (p < 0.01 vs. controls) and xenograft studies showed that the number of metastatic nodules in the lung surface was significantly lower in nude mice bearing xenografts with Notch-1 knockdown compared to those bearing control xenografts (p < 0.01 vs. controls).ConclusionNotch-1 knockdown suppresses the growth and migration of SACC cells in vitro and the metastasis of SACC cells in vivo. Notch-1 may be a new candidate target in SACC.

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Section: Resultsmentioning

confidence: 99%

“…Notch-1 was shown to promote the invasion and metastasis of esophageal carcinoma cells by inducing epithelial-mesenchymal transition (EMT) [ 14 ]. Activation of Notch-1 signaling was demonstrated in gefitinib-resistant lung cancer cells undergoing EMT [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Notch-1 knockdown suppresses proliferation, migration and metastasis of salivary adenoid cystic carcinoma cells

et al. 2015

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“…Previous studies have demonstrated that Jagged1-induced Notch signaling activation induces EMT through Slug-mediated repression of E-cadherin [ 35 ]. A recent study has shown that Notch1 mediates esophageal carcinoma cell invasion and metastasis by inducing EMT through upregulation of Snail [ 38 ]. Likewise, our study showed that the EMT process was closely related to Notch1 signaling in breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Notch1 signaling regulates the epithelial–mesenchymal transition and invasion of breast cancer in a Slug-dependent manner

et al. 2015

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BackgroundThe epithelial–mesenchymal transition (EMT) is crucial for the invasion and metastasis of breast cancer. However, how Notch signaling regulates the EMT process and invasion in breast cancer remains largely unknown.MethodsThe impact of Notch1 silencing by specific shRNAs on the EMT and invasion of human breast cancer MCF-7 and MDA-MB-231 cells as well as xenografts was tested by western blot, real-time polymerase chain reaction (RT-PCR), immunofluorescence, transwell, and immunohistochemistry assays. The effect of Slug silencing or upregulation on the EMT and invasion of breast cancer cells was analyzed, and the effect of Notch1 signaling on Slug expression was determined by the luciferase reporter assay.ResultsThe Notch1 intracellular domain (N1ICD) and Jagged1 were expressed in breast cancer cells. Notch1 silencing reversed the spontaneous EMT process and inhibited the migration and invasion of breast cancer cells and the growth of xenograft breast cancers. The expression of N1ICD was upregulated significantly by Jagged1-mediated Notch signaling activation. Moreover, Jagged1-mediated Notch signaling promoted the EMT process, migration, and invasion of breast cancer cells, which were abrogated by Notch silencing. Furthermore, the N1ICD positively regulated the Slug expression by inducing Slug promoter activation. Importantly, the knockdown of Slug weakened the invasion ability of breast cancer cells and reversed the Jagged1-induced EMT process with significantly decreased expression of vimentin and increased expression of E-cadherin. In addition, Slug overexpression restored the Notch1 knockdown-suppressed EMT process.ConclusionsOur novel data indicate that Notch signaling positively regulates the EMT, invasion, and growth of breast cancer cells by inducing Slug expression. The Notch1–Slug signaling axis may represent a potential therapeutic target for breast cancer therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-015-0295-3) contains supplementary material, which is available to authorized users.

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“…NOTCH1 expression was associated with cell aggressiveness and 5-FU drug resistance in ESCC patients [125]. NOTCH1 increased invasion and metastasis of ESCC cell line EC-9706 through EMT transducted by Snail [126]. High NOTCH1 protein expression was related to poor survival in ESCC [127].…”

Section: Introductionmentioning

confidence: 99%

NOTCH receptors in gastric and other gastrointestinal cancers: oncogenes or tumor suppressors?

et al. 2016

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Gastric cancer (GC) ranks the most common cancer types and is one of the leading causes of cancer-related death. Due to delayed diagnosis and high metastatic frequency, 5-year survival rate of GC is rather low. It is a complex disease resulting from the interaction between environmental factors and host genetic alterations that deregulate multiple signaling pathways. The Notch signaling pathway, a highly conserved system in the regulation of the fate in several cell types, plays a pivotal role in cell differentiation, survival and proliferation. Notch is also one of the most commonly activated signaling pathways in tumors and its aberrant activation plays a key role in cancer advancement. Whether Notch cascade exerts oncogenic or tumor suppressive function in different cancer types depends on the cellular context. Mammals have four NOTCH receptors that modulate Notch pathway activity. In this review, we provide a comprehensive summary on the functional role of NOTCH receptors in gastric and other gastrointestinal cancers. Increasing knowledge of NOTCH receptors in gastrointestinal cancers will help us recognize the underlying mechanisms of Notch signaling and develop novel therapeutic strategies for GC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-016-0566-7) contains supplementary material, which is available to authorized users.

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Notch-1-mediated esophageal carcinoma EC-9706 cell invasion and metastasis by inducing epithelial–mesenchymal transition through Snail

Cited by 22 publications

References 28 publications

Notch-1 knockdown suppresses proliferation, migration and metastasis of salivary adenoid cystic carcinoma cells

Notch-1 knockdown suppresses proliferation, migration and metastasis of salivary adenoid cystic carcinoma cells

Notch1 signaling regulates the epithelial–mesenchymal transition and invasion of breast cancer in a Slug-dependent manner

NOTCH receptors in gastric and other gastrointestinal cancers: oncogenes or tumor suppressors?

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