scholarly journals Aberrant Expression and Subcellular Localization of PER2 Promote the Progression of Oral Squamous Cell Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Fengyuan Guo ◽  
Qingming Tang ◽  
Guangjin Chen ◽  
Jiwei Sun ◽  
Junyi Zhu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Subcellular Localization ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Epithelial Mesenchymal Transition ◽  
Aberrant Expression ◽  
Mesenchymal Transition

Oral squamous cell carcinoma, one of the most prevalent cancer types in the world, has been confirmed under the influence of a key circadian gene, PER2, whose role has been identified in the development of some other types of cancers. However, the mechanism through which PER2 regulates the progress of OSCC remains largely unknown. In this study, we showed that besides the abnormal expression and subcellular localization of PER2 observed in OSCC tissues and cells as expected, these anomalous changes also existed in the adjacent noncancerous tissues, which was a novel finding in our research. The phase of PER2 rhythmic expression pattern in OSCC cells was later than that in oral keratinocytes in the protein level. In addition, we demonstrated that PER2 played as a resistant factor in the development of OSCC by upregulating TP53 and inhibiting epithelial-mesenchymal transition in vitro and in vivo. Taken together, our results identified that the development of OSCC is closely associated with PER2, the aberrant expression and subcellular localization of which facilitates the malignant progress.

scholarly journals FAP overexpression induce Epithelial-Mesenchymal Transition (EMT) in oral squamous cell carcinoma by down-regulating DPP9 gene

2019 ◽  
Author(s):  
Qing-qing Wu ◽  
Meng Zhao ◽  
Guang-zhao Huang ◽  
Ze-nan Zheng ◽  
Wei-sen Zeng ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Promoter ◽  
Tissue Samples ◽  
Mesenchymal Transition

AbstractFAP acts as a tumor promoter via epithelial-mesenchymal transition (EMT) in human oral squamous cell carcinoma (OSCC). The present study was designed to investigate the interaction proteins with FAP and explore the precise mechanism of FAP promoting EMT in OSCC. IP-MS analysis confirmed that DPP9 was an interacting protein of FAP. DPP9 was down-regulated in OSCC tissue samples compared with MNT using immunohistochemistry and quantitative-PCR detection. Lower DPP9 was correlated with unfavorable overall survival of patients with OSCC. Repressing DPP9 accelerates the proliferation of OSCC cells in vitro and in vivo. Mechanistically, overexpression of FAP downregulate the expression of the DPP9 and the effect of FAP on OSCC proliferation, migration, invasion and EMT could be reversed by up-regulated DPP9. Our study suggests that FAP could induce EMT and promote carcinogenesis in oral squamous cell carcinoma by down-regulating DPP9 gene. That will hint different dimension on therapy for patients with OSCC.

scholarly journals CCL18-induced LINC00319 promotes proliferation and metastasis in oral squamous cell carcinoma via the miR-199a-5p/FZD4 axis

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Xiao Jiang ◽  
Jingpeng Liu ◽  
Simin Li ◽  
Bo Jia ◽  
Zhijie Huang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
In Vivo Experiments ◽  
Oral Cancer Cells

Abstract Long non-coding RNAs (lncRNAs), which may be modulated by chemokines, are key regulators in many cancers including oral squamous cell carcinoma (OSCC). An understanding of lncRNAs involved in chemokine (CC motif) ligand 18 (CCL18)-induced OSCC promotion remains elusive. The present study using lncRNA sequencing found LINC00319 to be significantly upregulated in OSCC cells subjected to rCCL18 stimulation. Furthermore, LINC00319 knockdown was found to attenuate the carcinogenic function of CCL18 in OSCC, reducing OSCC proliferation, metastasis, epithelial-mesenchymal transition (EMT), and angiogenesis. LINC00319 was demonstrated to act as a ceRNA in OSCC, which directly responded to miR-199a-5p and rescued the repression of FZD4 by miR-199a-5p. Functionally, in vitro and in vivo experiments showed that LINC00319 promoted OSCC growth and metastasis via downregulating miR-199a-5p and upregulating FZD4. In vitro rescue assays demonstrated that miR-199a-5p inhibitor or FZD4 overexpression reversed the effects of LINC00319 silencing in OSCC. Importantly, the expression of miR-199a-5p and FZD4 were found to be mediated by CCL18, and miR-199a-5p mimics inhibited the CCL18-promoting effects in oral cancer cells. Taken together, these results evidenced a mechanism of CCL18 action in OSCC mediated through the LINC00319/miR-199a-5p/FZD4 signaling pathway, which may comprise a potential target for OSCC therapeutic development.

scholarly journals PDK1 Inhibitor BX795 Improves Cisplatin and Radio-Efficacy in Oral Squamous Cell Carcinoma by Downregulating the PDK1/CD47/Akt-Mediated Glycolysis Signaling Pathway

2021 ◽  
Vol 22 (21) ◽  
pp. 11492
Author(s):  
Shin Pai ◽  
Vijesh Kumar Yadav ◽  
Kuang-Tai Kuo ◽  
Narpati Wesa Pikatan ◽  
Chun-Shu Lin ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Strategies ◽  
Metabolic Reprogramming ◽  
Combination Group ◽  
Aberrant Expression ◽  
Mesenchymal Transition

Background: Oral squamous cell carcinoma (OSCC) has a high prevalence and predicted global mortality rate of 67.1%, necessitating better therapeutic strategies. Moreover, the recurrence and resistance of OSCC after chemo/radioresistance remains a major bottleneck for its effective treatment. Molecular targeting is one of the new therapeutic approaches to target cancer. Among a plethora of targetable signaling molecules, PDK1 is currently rising as a potential target for cancer therapy. Its aberrant expression in many malignancies is observed associated with glycolytic re-programming and chemo/radioresistance. Methods: Furthermore, to better understand the role of PDK1 in OSCC, we analyzed tissue samples from 62 patients with OSCC for PDK1 expression. Combining in silico and in vitro analysis approaches, we determined the important association between PDK1/CD47/LDHA expression in OSCC. Next, we analyzed the effect of PDK1 expression and its connection with OSCC orosphere generation and maintenance, as well as the effect of the combination of the PDK1 inhibitor BX795, cisplatin and radiotherapy in targeting it. Results: Immunohistochemical analysis revealed that higher PDK1 expression is associated with a poor prognosis in OSCC. The immunoprecipitation assay indicated PDK1/CD47 binding. PDK1 ligation significantly impaired OSCC orosphere formation and downregulated Sox2, Oct4, and CD133 expression. The combination of BX795 and cisplatin markedly reduced in OSCC cell’s epithelial-mesenchymal transition, implying its synergistic effect. p-PDK1, CD47, Akt, PFKP, PDK3 and LDHA protein expression were significantly reduced, with the strongest inhibition in the combination group. Chemo/radiotherapy together with abrogation of PDK1 inhibits the oncogenic (Akt/CD47) and glycolytic (LDHA/PFKP/PDK3) signaling and, enhanced or sensitizes OSCC to the anticancer drug effect through inducing apoptosis and DNA damage together with metabolic reprogramming. Conclusions: Therefore, the results from our current study may serve as a basis for developing new therapeutic strategies against chemo/radioresistant OSCC.

scholarly journals Inactivation of GSK3β and activation of NF-κB pathway via Axl represents an important mediator of tumorigenesis in esophageal squamous cell carcinoma

2015 ◽  
Vol 26 (5) ◽  
pp. 821-831 ◽  
Author(s):  
Juliano D. Paccez ◽  
Kristal Duncan ◽  
Akhona Vava ◽  
Ricardo G. Correa ◽  
Towia A. Libermann ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Epithelial Mesenchymal Transition ◽  
Glycogen Synthase ◽  
Mesenchymal Transition ◽  
Therapeutic Implications

Deregulation of Axl in esophageal squamous cell carcinoma (OSCC) with potential therapeutic implications is described for the first time. This paper also sheds light on the understanding of how Axl regulates OSCC development in vitro and in vivo. Axl expression leads to an Akt-dependent regulation of glycogen synthase kinase 3β activity and the nucluear factor kappaB (NF-κB) pathway, affecting the epithelial–mesenchymal transition.

scholarly journals Ephrin A4-ephrin receptor A10 signaling promotes cell migration and spheroid formation by upregulating NANOG expression in oral squamous cell carcinoma cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu-Lin Chen ◽  
Yi-Chen Yen ◽  
Chuan-Wei Jang ◽  
Ssu-Han Wang ◽  
Hsin-Ting Huang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Migration ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Promising Therapeutic Approach ◽  
Sphere Formation

AbstractEphrin type-A receptor 10 (EPHA10) has been implicated as a potential target for breast and prostate cancer therapy. However, its involvement in oral squamous cell carcinoma (OSCC) remains unclear. We demonstrated that EPHA10 supports in vivo tumor growth and lymphatic metastasis of OSCC cells. OSCC cell migration, epithelial mesenchymal transition (EMT), and sphere formation were found to be regulated by EPHA10, and EPHA10 was found to drive expression of some EMT- and stemness-associated transcription factors. Among EPHA10 ligands, exogenous ephrin A4 (EFNA4) induced the most OSCC cell migration and sphere formation, as well as up-regulation of SNAIL, NANOG, and OCT4. These effects were abolished by extracellular signal-regulated kinase (ERK) inhibition and NANOG knockdown. Also, EPHA10 was required for EFNA4-induced cell migration, sphere formation, and expression of NANOG and OCT4 mRNA. Our microarray dataset revealed that EFNA4 mRNA expression was associated with expression of NANOG and OCT4 mRNA, and OSCC patients showing high co-expression of EFNA4 with NANOG or OCT4 mRNA demonstrated poor recurrence-free survival rates. Targeting forward signaling of the EFNA4-EPHA10 axis may be a promising therapeutic approach for oral malignancies, and the combination of EFNA4 mRNA and downstream gene expression may be a useful prognostic biomarker for OSCC.

scholarly journals Effects of lentivirus-mediated shRNA targeting integrin-linked kinase on oral squamous cell carcinoma in vitro and in vivo

2015 ◽  
Vol 35 (1) ◽  
pp. 89-98 ◽  
Author(s):  
LIN QUE ◽  
DAN ZHAO ◽  
XIU-FA TANG ◽  
JI-YUAN LIU ◽  
XIANG-YU ZHANG ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Integrin Linked Kinase

scholarly journals Synergetic Effects of PARP Inhibitor AZD2281 and Cisplatin in Oral Squamous Cell Carcinoma in Vitro and in Vivo

2016 ◽  
Vol 17 (3) ◽  
pp. 272 ◽  
Author(s):  
Masaaki Yasukawa ◽  
Hisako Fujihara ◽  
Hiroaki Fujimori ◽  
Koji Kawaguchi ◽  
Hiroyuki Yamada ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Parp Inhibitor ◽  
Synergetic Effects
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