Epiregulin Promotes Lung Metastasis of Salivary Adenoid Cystic Carcinoma

Yang, Wenwen; Yang, Lin-Qian; Zhao, Fei; Chen, Chuwen; Xu, Lihua; Fu, Jia; Li, Shenglin; Ge, Xi‐Yuan

doi:10.7150/thno.19712

Cited by 67 publications

(76 citation statements)

References 43 publications

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“…Similarly, in the current study, MYB significantly enhanced SACC cell migration and invasion in in vivo and in vitro experiments. Previous studies demonstrated that VEGF promoted metastasis via angiogenesis (24,25,47). The current study demonstrated that VEGFA was upregulated in MYB overexpressing SACC cells, indicating that MYB could increase the metastasis of SACC cells by increasing VEGFA expression.…”

Section: Discussionsupporting

confidence: 54%

“…5A). ICAM1, VEGFA, MMP7 and MMP9, which are involved in cell migration and invasion (24,25,35,36), were upregulated following MYB overexpression. In addition, CCND1, MCL1, ICAM1, VEGFA, MMP7 and MMP9 were downregulated, whereas p21 was upregulated following MYB knockdown (Fig.…”

Section: Myb Promotes Sacc Lung Metastasis In Vivomentioning

confidence: 97%

“…Changes in cellular morphology and phenotypic characteristics facilitate epithelial cell transformation into cells with mesenchymal features, which gain an invasive phenotype and stronger motility (22)(23)(24). During EMT, the expression of cell adhesion molecules, such as cadherin-1 (E-cadherin, encoded by CDH1), decrease, and the expression of mesenchymal markers, including vimentin (encoded by VIM) and cadherin-2 (N-cadherin, encoded by CDH2), increase (25). MYB has been reported to enhance breast cancer metastasis by activating the Wnt/catenin β-1 (β-catenin)/Axin-2 signalling pathway, which is one of the most important pathways that leads to EMT activation.…”

Section: Myb Promotes the Growth And Metastasis Of Salivary Adenoid Cmentioning

confidence: 99%

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MYB promotes the growth and metastasis of salivary adenoid cystic carcinoma

Zhao

Yang

et al. 2019

Int J Oncol

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The incidence of recurrent t(6;9) translocation of the MYB proto-oncogene to NFIB (the gene that encodes nuclear factor 1 B-type) in adenoid cystic carcinoma (ACC) tumour tissues is high. However, MYB [the gene that encodes transcriptional activator Myb (MYB)] overexpression is more common, indicating that MYB serves a key role in ACC. The current study aimed to investigate the role of MYB in salivary (S)ACC growth and metastasis. A total of 50 fresh-frozen SACC tissues and 41 fresh-frozen normal submandibular gland (SMG) tissues were collected to measure MYB mRNA expression, and to analyse the associations between MYB and epithelial-mesenchymal transition (EMT) markers. Compared with normal SMG tissue, SACC tissues demonstrated significantly increased MYB expression, with a high expression rate of 90%. Interestingly, MYB tended to be negatively correlated with CDH1 [the gene that encodes cadherin-1 (E-cadherin)] and positively correlated with VIM (the gene that encodes vimentin), suggesting that MYB is associated with SACC metastasis. To explore the role of MYB in SACC, the authors stably overexpressed and knocked down MYB in SACC cells. The authors of the current study demonstrated that MYB overexpression promoted SACC cell proliferation, migration and invasion, whereas its knockdown inhibited these activities. Additionally, when MYB was overexpressed, CDH1 expression was downregulated, and CDH2 (the gene that encodes cadherin-2), VIM and ACTA2 (the gene that encodes actin, aortic smooth muscle) expression was upregulated. Then, the effect of MYB on lung tumour metastasis was investigated in vivo in non-obese diabetic/severe combined immunodeficiency mice. MYB overexpressing and control cells were injected into the mice through the tail vein. The results revealed that MYB promoted SACC lung metastasis. Collectively, these results demonstrated that MYB is aberrantly overexpressed in SACC tissues, and promotes SACC cell proliferation and metastasis, indicating that MYB may be a novel therapeutic target for SACC.

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Section: Discussionsupporting

confidence: 54%

Section: Myb Promotes Sacc Lung Metastasis In Vivomentioning

confidence: 97%

Section: Myb Promotes the Growth And Metastasis Of Salivary Adenoid Cmentioning

confidence: 99%

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MYB promotes the growth and metastasis of salivary adenoid cystic carcinoma

Zhao

Yang

et al. 2019

Int J Oncol

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“…As a result, the survival rates after a diagnosis of SACC are 35% at 5 years, 15% at 10 years, and 0% at 15 years, which points to the poor outcomes of the tumor [3]. Due to the poor understanding of the mechanism of SACC progression, no effective therapy has been provided [5]. Therefore, it is impending to define the underlying mechanism of SACC and to explore the methods for SACC treatment.…”

Section: Introductionmentioning

confidence: 99%

The NOTCH1-HEY1 pathway regulates self-renewal and epithelial-mesenchymal transition of salivary adenoid cystic carcinoma cells

et al. 2020

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Our previous study demonstrated a close relationship between the NOTCH signaling pathway and salivary adenoid cystic carcinoma (SACC). Its receptor gene, NOTCH1, and its downstream gene, HES1, contribute to the proliferation, invasion and metastasis of SACC. Accumulating evidence supports HEY1 as another effector of the signaling pathway. The purpose of this study was to explore the effects of the NOTCH1-HEY1 pathway on the proliferation, invasion and metastasis of SACC cells. Our results verified that HEY1 is a specific molecular target of the NOTCH signaling pathway in SACC cells and that its expression in carcinoma is much higher than that in paracarcinoma tissues. The expression of NOTCH1 and HEY1 are positively correlated in the salivary adenoid cystic carcinoma tissues. NOTCH1 is significantly related to the activation of HEY1 in SACC, and that HEY1 reciprocally regulates NOTCH1 expression in SACC. HEY1 promotes cell proliferation and spheroid formation and inhibits cell apoptosis in vitro. In addition, HEY1 enhances the tumorigenicity of SACC in vivo. Furthermore, HEY1 increases cell invasion and metastasis by driving the expression of epithelial-mesenchymal transition (EMT)-related genes and MMPs. The results of this study indicate that the NOTCH1-HEY1 pathway is specifically upregulated in SACC and promotes cell proliferation, self-renewal, invasion, metastasis and the expression of EMT-related genes and MMPs. Our findings suggest that a NOTCH1-HEY1 pathway inhibitor might therefore have potential therapeutic applications in treating SACC patients by inhibiting cancer cell growth and metastasis.

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“…The RhoG/Rac1 signaling pathway was also involved in the epiregulin‐induced migration and invasion of SACC cells. Epiregulin can significantly induce SACC cell migration and invasion and is closely related to lung metastasis (Hu et al, ; Yang et al, ). However, its downstream effectors remain to be fully understood.…”

Section: Discussionmentioning

confidence: 99%

RhoG/Rac1 signaling pathway involved in migration and invasion of salivary adenoid cystic carcinoma cells

Hao

Gan

2019

Oral Diseases

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Objectives This study aimed to explore whether RhoG/Rac1 was involved in migration and invasion of salivary adenoid cystic carcinoma (SACC). Materials and Methods RhoG and Rac1 were evaluated in two SACC cell lines, namely SACC‐83 and SACC‐LM, with low and high rates of lung metastasis, respectively. Functional changes were evaluated using cell proliferation, transwell, and wound‐healing assays, and molecular events were investigated using real‐time PCR and Western blot assays. Results RhoG and Rac1 were highly expressed and more activated in SACC‐LM cells than in SACC‐83 cells. RhoG overexpression promoted SACC‐83 cell migration and invasion through activating Rac1. The knockdown of RhoG or Rac1 partially blocked epiregulin‐induced migration and invasion in SACC‐83 cells. Epiregulin‐induced activation of RhoG/Rac1 in SACC‐83 cells was blocked by a Src inhibitor, or an AKT inhibitor or AKT siRNA, or an ERK1/2 inhibitor. Moreover, the epiregulin‐induced phosphorylation of AKT and ERK1/2 in SACC‐83 cells was blocked by a Src inhibitor, and the epiregulin‐induced phosphorylation of ERK1/2 was blocked by an AKT inhibitor or AKT siRNA. Overexpression of activated AKT induced activation of ERK1/2 and RhoG. Conclusions RhoG/Rac1 signaling pathway was involved in SACC cell migration and invasion. RhoG/Rac1 at least partially mediated epiregulin/Src/AKT/ERK1/2 signaling to promote SACC cell migration and invasion.

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Epiregulin Promotes Lung Metastasis of Salivary Adenoid Cystic Carcinoma

Cited by 67 publications

References 43 publications

MYB promotes the growth and metastasis of salivary adenoid cystic carcinoma

MYB promotes the growth and metastasis of salivary adenoid cystic carcinoma

The NOTCH1-HEY1 pathway regulates self-renewal and epithelial-mesenchymal transition of salivary adenoid cystic carcinoma cells

RhoG/Rac1 signaling pathway involved in migration and invasion of salivary adenoid cystic carcinoma cells

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