Epiregulin promotes migration and invasion of salivary adenoid cystic carcinoma cell line SACC-83 through activation of ERK and Akt

Kai, Hu; Li, Shenglin; Gan, Ye‐Hua; Wang, Cun‐Yu; Yu, Guang-yan

doi:10.1016/j.oraloncology.2008.04.009

Cited by 50 publications

(49 citation statements)

References 36 publications

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“…pAkt may be involved in invasion by head and neck squamous cell carcinoma [33,34] . Gal-3-mediated cancer cell invasion occurs not only through Akt but also through other effectors that are regulated by Gal-3 and the Wnt/β-catenin signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Galectin-3 gene silencing inhibits migration and invasion of human tongue cancer cells in vitro via downregulating β-catenin

et al. 2012

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Aim: Galectin-3 (Gal-3) is a member of the carbohydrate-binding protein family that contributes to neoplastic transformation, tumor survival, angiogenesis, and metastasis. The aim of this study is to investigate the role of Gal-3 in human tongue cancer progression. Methods: Human tongue cancer cell lines (SCC-4 and CAL27) were transfected with a small-interfering RNA against Gal-3 (Gal-3-siRNA). The migration and invasion of the cells were examined using a scratch assay and BD BioCoat Matrigel Invasion Chamber, respectively. The mRNA and protein levels of β-catenin, Akt/pAkt, GSK-3β/pGSK-3β, MMP-9 in the cells were measured using RT-PCR and Western blotting, respectively. Results: Transient silencing of Gal-3 gene for 48 h significantly suppressed the migration and invasion of both SCC-4 and CAL27 cells. Silencing of Gal-3 gene significantly decreased the protein level of β-catenin, leaving the mRNA level of β-catenin unaffected. Furthermore, silencing Gal-3 gene significantly decreased the levels of phosphorylated Akt and GSK-3β, and suppressed the mRNA and protein levels of MMP-9 in the cells. Conclusion: Our data suggest that Gal-3 mediates the migration and invasion of tongue cancer cells in vitro via regulating the Wnt/ β-catenin signaling pathway and Akt phosphorylation.

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Section: Discussionmentioning

confidence: 99%

Galectin-3 gene silencing inhibits migration and invasion of human tongue cancer cells in vitro via downregulating β-catenin

et al. 2012

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“…34 Both cell lines were cultured in RPMI 1640 complete medium with 10% inactivated FBS, 200 000 U/l penicillin, and 200 000 U/l streptomycin in humidified 5% CO 2 …”

Section: Cell Culture and Tumor Specimensmentioning

confidence: 99%

miR-21 regulates tumor progression through the miR-21-PDCD4-Stat3 pathway in human salivary adenoid cystic carcinoma

Jiang

Hou

et al. 2015

Laboratory Investigation

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miR-21, which is a putative tumor onco-miR and frequently overexpressed microRNA in various tumors, has been linked to tumor progression through targeting of tumor-suppressor genes. In this study, we sought to determine whether miR-21 has any role on tumor progression of salivary adenoid cystic carcinoma (SACC) and the possible mechanisms. We found that the level of miR-21 expression was significantly higher in SACC than that in normal salivary tissues, and it is also higher in tumors with metastasis than that without metastasis. Using an anti-miR-21 inhibitor in an in vitro model, downregulation of miR-21 significantly decreased the capacity of invasion and migration of SACC cells, whereas a pre-miR-21 increased the capacity of invasion and migration of SACC cells. To explore the potential mechanisms by which miR-21 regulate invasion and migration, we identified one direct miR-21 target gene, programmed cell death 4 (PDCD4), which has been implicated in invasion and metastasis Salivary adenoid cystic carcinoma (SACC) is one of the most common malignancy of the salivary gland, accounting for 10% of salivary gland tumors and 30% of human salivary gland malignancies. 1,2 SACC is characterized by slow but aggressive growth, nerve and blood vessel invasion, multiple recurrences, and distant metastases. 3-5 Lung metastasis and nerve metastasis are the biological characteristics of SACC. [6][7][8] It has been reported that the incidence of SACC with distant metastasis ranged from 35 to 50% of all cases. Lung was the most common organ of its distant metastasis, and lung metastasis is still the leading death cause of patients with SACC. 4,5 Although the 5-year survival rate is high for patients with SACC, probably because of the slow growth of the tumor, the 10-and 15-year prognoses are poor because of the frequent local recurrences and distant metastases. [6][7][8] Although multiple genetic and epigenetic alterations have been detected in SACC, 3,9-13 the precise molecular mechanisms of progression and metastasis of SACC remain unknown.MicroRNAs (miRNAs) are small non-coding RNA molecules, with a length of 20-22 nucleotides, that regulate gene expression by either translational inhibition or mRNA degradation. miRNAs function as either oncogenes or tumor suppressors by inhibiting the expression of target genes, some of which are either directly or indirectly involved with canonical signaling pathways. 13,14 The roles and function of some selected miRNAs in SACC have been reported. 15

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“…In many human cancers, EREG is overexpressed, and promotes cell growth and migration. 37,38 EREG also increases cell differentiation and survival. However, some studies have shown that EREG inhibits the growth of tumor-derived epithelial cell lines.…”

Section: Discussionmentioning

confidence: 98%

Gene silencing of EREG mediated by DNA methylation and histone modification in human gastric cancers

Yun

Song

Park

et al. 2012

Laboratory Investigation

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Epiregulin (EREG) induces cell growth by binding to the epidermal growth factor receptor (EGFR). Expression of EREG affects sensitivity to cetuximab a chimeric monoclonal antibody that inhibits the EGFR signaling pathway. The mechanism through which EREG is regulated is largely unknown, but a methyl-array study previously performed by our group revealed that EREG is methylated in gastric cancer cells. In this study, we found that EREG gene expression was low in 7 out of 11 gastric cancer cells and this downregulation was mediated by aberrant CpG methylation of the EREG promoter. Treatment with 5-aza-CdR restored EREG expression and demethylated CpG sites in the EREG promoter. Compared with DNA methyltransferase 1 (DNMT1), knock-down of DNA methyltransferase 3b (DNMT3b) significantly increased the expression of EREG and led to the demethylation of specific CpG sites in the EREG promoter, suggesting that DNMT3b primarily regulates CpG methylation and silencing of the EREG gene. EREG methylation was observed in 30% (4/13) of human primary gastric tumor tissues we evaluated. In addition to DNA methylation, results from a chromatin immunoprecipitation assay demonstrated that transcriptional levels of EREG were associated with the enrichment of active histone marks (H3K4me3 and AcH3) and of a repressive mark (H3K27me2). Treatment with 5-aza-CdR dynamically increased the low occupancy of H3K4me3 and AcH3, while decreasing the high enrichment of H3K27me2, indicating that dynamic histone modifications contribute to EREG regulation in addition to DNA methylation. Finally, the combination of 5-aza-CdR and cetuximab exerted a synergistic anti-proliferative effect on gastric cancer cells. Taken together, the results of our study showed for the first time that EREG is epigenetically silenced in gastric cancer cells by aberrant DNA methylation and histone modification.

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Epiregulin promotes migration and invasion of salivary adenoid cystic carcinoma cell line SACC-83 through activation of ERK and Akt

Cited by 50 publications

References 36 publications

Galectin-3 gene silencing inhibits migration and invasion of human tongue cancer cells in vitro via downregulating β-catenin

Galectin-3 gene silencing inhibits migration and invasion of human tongue cancer cells in vitro via downregulating β-catenin

miR-21 regulates tumor progression through the miR-21-PDCD4-Stat3 pathway in human salivary adenoid cystic carcinoma

Gene silencing of EREG mediated by DNA methylation and histone modification in human gastric cancers

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