Vimentin is a potential prognostic factor for tongue squamous cell carcinoma among five epithelial–mesenchymal transition-related proteins

MicroRNAs (miRNAs) regulate gene expression and at the same time mediate tumorigenesis. miR-373-3p has diverse effects in tumors, but its role in tongue squamous cell carcinoma (TSCC) remains unknown. The purpose of this study is to determine the function of miR-373-3p in the progression of TSCC. Our results brought to light that miR-373-3p is markedly upregulated in clinical TSCC tissues compared with paired adjacent normal tissues and has significant correlation with a more aggressive TSCC phenotype in patients. Gain-of-function and loss-of-function studies revealed that ectopic miR-373-3p overexpression promoted the metastasis of TSCC cells. Notably, Wnt/β-catenin signaling was hyperactivated in TSCC cells overexpressing miR-373-3p, and this pathway was responsible for the epithelial-mesenchymal transition (EMT) induced by miR-373-3p. Furthermore, miR-373-3p directly targeted and suppressed Dickkopf-1 (DKK1), a negative regulator of the Wnt/β-catenin signaling cascade. These results demonstrate that, by directly targeting DKK1, miR-373-3p constitutively activated Wnt/β-catenin signaling, thus promoting the EMT-induced metastasis of TSCC. Taken together, our findings reveal a new regulatory mechanism for miR-373-3p and suggest that miR-373-3p might be a potential target in TSCC therapy.

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FGF1–FGFR1 axis promotes tongue squamous cell carcinoma (TSCC) metastasis through epithelial–mesenchymal transition (EMT)

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2015.09.021 ◽

2015 ◽

Vol 466 (3) ◽

pp. 327-332 ◽

Cited By ~ 15

Author(s):

Jiuyang Jiao ◽

Xiaopeng Zhao ◽

Yancan Liang ◽

Dongxiao Tang ◽

Chaobin Pan

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Epithelial Mesenchymal Transition ◽

Tongue Squamous Cell Carcinoma ◽

Mesenchymal Transition

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Deregulation of Hexokinase II Is Associated with Glycolysis, Autophagy, and the Epithelial-Mesenchymal Transition in Tongue Squamous Cell Carcinoma under Hypoxia

BioMed Research International ◽

10.1155/2018/8480762 ◽

2018 ◽

Vol 2018 ◽

pp. 1-15 ◽

Cited By ~ 9

Author(s):

Guanhui Chen ◽

Yadong Zhang ◽

Jianfeng Liang ◽

Wenqing Li ◽

Yue Zhu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Epithelial Mesenchymal Transition ◽

Lactate Production ◽

Glucose Consumption ◽

Tongue Squamous Cell Carcinoma ◽

Migration And Invasion ◽

Control Group ◽

Mesenchymal Transition

The glycolytic enzyme Hexokinase (HKII) participates in tumor glycolysis and the progression of various cancers, but its clinicopathological effect on the progression of tongue squamous cell carcinoma (TSCC) and its role in glycolysis, autophagy, and the epithelial-mesenchymal transition of TSCC in a hypoxic microenvironment remain unknown. Our results showed that HKII expression was dramatically increased in TSCC tissues and that its upregulation was significantly associated with the presence of pathological differentiation, lymph node metastasis, and clinical stage. The level of autophagy-specific protein LC3, EMT-related proteins, and the migration and invasion capabilities of TSCC cells all increased under hypoxia. Moreover, hypoxia increased the glucose consumption and lactate production of TSCC cells, and we demonstrated that the expression of the glycolytic key gene HKII was significantly higher than in that of the control group. Notably, the downregulation of HKII resulted in a significant decrease of TSCC cell glucose consumption lactate production and autophagic activity during hypoxia. HKII knockdown blocked the migratory and invasive capacity of TSCC cells and we specifically determined that the EMT ability decreased. Therefore, our findings revealed that the upregulation of HKII enhanced glycolysis and increased autophagy and the epithelial-mesenchymal transition of tongue squamous cell carcinoma under hypoxia.

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Antioral Squamous Cell Carcinoma Effects of Carvacrol via Inhibiting Inflammation, Proliferation, and Migration Related to Nrf2/Keap1 Pathway

BioMed Research International ◽

10.1155/2021/6616547 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Hui Liu ◽

Xiaoliang Xu ◽

Ran Wu ◽

Lei Bi ◽

Chunguang Zhang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Molecular Mechanisms ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

And Migration ◽

Related Proteins ◽

Proliferation And Migration ◽

E Cadherin

Objective. To observe the therapeutic effect of Carvacrol on oral squamous cell carcinoma (OSCC) and dissect underlying molecular mechanisms. Methods. Keap1/Nrf2, NALP3, Vimentin, and E-cadherin expression was detected in OSCC and normal oral mucosa (NOM) tissues using immunofluorescence or western blot. When treated with Carvacrol or tert-butylhydroquinone (TBHQ) that activates Nrf2, the expression of Keap1/Nrf2/HO-1, epithelial-mesenchymal transition- (EMT-) related proteins, and NALP3 was examined in OSCC cells. Nrf2 was silenced by treatment with sh-Nrf2 or ML385. After silencing Nrf2 or Carvacrol treatment, cell proliferation and migration were assessed by clone formation and scratch and transwell tests in OSCC cells. Moreover, the expression of Keap1/Nrf2/HO-1, EMT-related proteins, and NALP3 was detected. Results. Keap1/Nrf2, NALP3, Vimentin, and E-cadherin proteins were all significantly upregulated in OSCC than NOM tissues. Carvacrol significantly suppressed Keap1/Nrf2/HO-1 activation. Carvacrol or silencing Nrf2 markedly inhibited the expression of Keap1/Nrf2/HO-1, EMT-related proteins, and NALP3 inflammasome in OSCC cells. Furthermore, clone formation and migration capacities were suppressed following treatment with Carvacrol or Nrf2 depletion. The opposite results were found when there is overexpression of Nrf2. However, Carvacrol distinctly improved the cancer-promoting effect induced by Nrf2 overexpression. Conclusion. Our findings suggested that Carvacrol ameliorated inflammation, proliferation, and migration for OSCC, which was related to inhibition of the Nrf2/Keap1 pathway.

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[Corrigendum] Epithelial mesenchymal transition induced by the CXCL9/CXCR3 axis through AKT activation promotes invasion and metastasis in tongue squamous cell carcinoma

Oncology Reports ◽

10.3892/or.2020.7883 ◽

2020 ◽

Vol 45 (2) ◽

pp. 791-792

Author(s):

Ziliang Li ◽

Jianqi Liu ◽

Lei Li ◽

Shuai Shao ◽

Jianhua Wu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Epithelial Mesenchymal Transition ◽

Tongue Squamous Cell Carcinoma ◽

Invasion And Metastasis ◽

Mesenchymal Transition ◽

Akt Activation

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LGR5 promotes invasion and migration by regulating YAP activity in hypopharyngeal squamous cell carcinoma cells

10.21203/rs.3.rs-28540/v1 ◽

2020 ◽

Author(s):

Zijia Zhu ◽

Shuyuan Yu ◽

Jihong Wen ◽

Ping Wang

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Epithelial Mesenchymal Transition ◽

Tumor Proliferation ◽

Mesenchymal Transition ◽

Hypopharyngeal Squamous Cell Carcinoma ◽

Inflammatory Microenvironment ◽

Lgr5 Expression ◽

Related Proteins

Abstract Background High leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) expression caused by an inflammatory microenvironment was reported to promote tumor proliferation and the epithelial–mesenchymal transition (EMT) in various malignant tumors, but those effects have not been studied in hypopharyngeal squamous cell carcinoma (HSCC) and the molecular mechanism remains unclear. Additionally, YAP/TAZ, an upstream or downstream factor of multiple signaling pathways, can promote tumor proliferation, invasion, and angiogenesis. Our study was aimed to determine whether YAP/TAZ is involved in the regulation of LGR5 expression in the inflammatory microenvironment.Methods We stimulated FaDu cells, a hypopharyngeal squamous cell carcinoma cell line, with inflammatory medium. The expression levels of EMT-related proteins, LGR5, and p-YAP were detected by reverse transcription–polymerase chain reaction, western blotting, and immunofluorescence.Results The results showed that LGR5 expression and the EMT process were significantly enhanced. The expression of EMT-related proteins was up-regulated, while that of p-YAP was decreased. After inhibiting the high LGR5 expression with short interfering RNA, the expression of EMT-related proteins was also down-regulated, while that of p-YAP was significantly increased. The use of verteporfin (VP), an inhibitor of YAP activity that promotes YAP phosphorylation, did not affect LGR5 expression.Conclusions Our findings suggest that the inflammatory microenvironment leads to high LGR5 expression, up-regulating the expression of EMT-related proteins by inhibiting the YAP phosphorylation.

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