The Role of E-Cadherin Down-Regulation in Oral Cancer: CDH1 Gene Expression and Epigenetic Blockage

Pannone, Giuseppe; Santoro, Angela; Feola, Antonia; Bufo, Pantaleo; Papagerakis, Pétros; Muzio, Lorenzo Lo; Staibano, S.; Ionna, Franco; Longo, Francesco; Franco, Renato; Aquino, Gabriella; Contaldo, María; Maria, S. De; Serpico, Rosario; Rosa, Alessandro; Rubini, Corrado; Papagerakis, Silvana; Giovane, Alfonso; Tombolini, Vincenzo; Giordano, A.; Caraglia, Michele; Domenico, Marina Di

doi:10.2174/1568009613666131126115012

Cited by 53 publications

(52 citation statements)

References 31 publications

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“…The loss of E-cadherin expression is a crucial step in the epithelial-mesenchymal transition (EMT) and is involved in cancer invasion and metastasis [61]. In human tumors, E-cadherin down-regulation is frequently associated with poor prognosis [62,63]. Interestingly, MTA2 promotes NSCLC metastasis through E-cadherin inhibition [64].…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

ITRAQ-Based Proteomics Analysis of Triptolide On Human A549 Lung Adenocarcinoma Cells

Zhao

Yang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Triptolide (TP) is a diterpenoid triepoxide extracted from the traditional Chinese medical herb Tripterygium wilfordii that exerts prominent broad-spectrum anticancer activity to repress proliferation and induce cancer cell apoptosis through various molecular pathways. We previously observed that TP inhibits the progression of A549 cells and pancreatic cancer cells (PNCA-1) in vitro. However, the complex molecular mechanism underlying the anticancer activity of TP is not well understood. Methods: To explore the molecular mechanisms by which TP induces lung cancer cell apoptosis, we investigated changes in the protein profile of A549 cells treated with TP using a proteomics approach (iTRAQ [isobaric tags for relative and absolute quantitation] combined with NanoLC-MS/MS [nano liquid chromatographymass spectrometry]). Changes in the profiles of the expressed proteins were analyzed using the bioinformatics tools OmicsBean and the Kyoto Encyclopedia of Genes and Genomes (KEGG) and were verified using western blotting. Apoptosis and cell cycle effects were analyzed using flow cytometry. Results: TP induced apoptosis in A549 cells and blocked A549 cells at the G2/M phase. Using iTRAQ technology, we observed 312 differentially expressed proteins associated in networks and implicated in different KEGG pathways. Gene Ontology (GO) analysis showed the overviews of dysregulated proteins in the biological process (BP), cell component (CC), and molecular function (MF) categories. Moreover, some candidate proteins involved in PARP1/AIF and nuclear Akt signaling pathways or metastasis processes were validated by western blotting. Conclusion: TP exerted anti-tumor activity on non-small cell lung cancer (NSCLC) A549 lung adenocarcinoma cells by dysregulating tumor-related protein expression. Herein, we provide a preliminary study of TP-related cytotoxicity on A549 cells using proteomics tools. These findings may improve the current understanding of the anti-tumor effects of TP on lung cancer cells and may reveal candidate proteins as potential targets for the treatment of lung cancer.

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Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

ITRAQ-Based Proteomics Analysis of Triptolide On Human A549 Lung Adenocarcinoma Cells

Zhao

Yang

et al. 2018

Cell Physiol Biochem

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“…In liver cancer, the sickness generally develops in the setting of chronic liver disease, in which continuous inflammation and hepatocyte regeneration occur. These processes, common to other tumor subtypes [17], include also the expansion of stem/progenitor cells, accumulation of genetic and/or epigenetic mutations, and alterations of the microenvironment (Figure 2A, B). Hepatic stem cells are markedly elevated in chronic liver disease [18].…”

Section: Introductionmentioning

confidence: 99%

Expression of cancer stem cell biomarkers as a tool for a correct therapeutic approach to hepatocellular carcinoma

et al. 2015

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Liver cancer is the fifth most commonly diagnosed malignancy and the second most frequent cause of cancer death in men worldwide. Amongst liver cancers, hepatocellular carcinoma (HCC) represents the major histological subtype and it is one of the most common malignant human tumors worldwide. Research into the molecular biology of hepatocarcinogenesis has identified several biomarkers, which could provide additional informations in order to better understand the biology of HCC. A large number of biomarkers have been shown to have potential predictive significance and a wide variety of molecular markers have been proven to be excellent diagnostic tools for HCC but it is difficult to characterize HCC with a single biomarker. Thus, signatures of a combination of biomarkers may be more valuable for the diagnosis, staging and prognosis of HCC. Specifically, a correlation of HCC-CSCs phenotype to specific hepatic cancer subtypes and to specific clinical and pathological features has not yet been reported in human liver tumors. In this view we will first discuss the possible sources of liver stem cells and their relation with liver cancer development and we will secondly focus on the prognostic significance of clinical and pathological features of HCC.

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“…The delocalized E-cadherin was assessed as previously described. 3 Differences between groups were determined using the one-way analysis of variance (ANOVA) and Scheffé test for pairwise comparisons.…”

Section: Tissue Microarray Based Double Staining Immunohistochemistrymentioning

confidence: 99%

“…1 proteolysis. We have previously showed that low E-Cadherin expression and/or its delocalization from membrane to cytoplasm, likely due to the hypermethylation of CDH1 promoter or to the increased expression of EGFR, is a negative prognostic factor in OSCC 3. The induction of transcriptional repressors, such as Snail, SLUG and ZEB family members, by certain microRNAs (miR-200 and miR-205), is able to determine EMT and the enrolment/action of "mesenchymal" cadherins 4.…”

mentioning

confidence: 99%

Expression and clinical implication of cyclooxygenase-2 and E-cadherin in oral squamous cell carcinomas

Santoro

Bufo

Russo

et al. 2020

Cancer Biology & Therapy

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Epithelial-Mesenchymal Transition (EMT) and angiogenesis are crucial events for development of aggressive and often fatal Oral Squamous Cell Carcinomas (OSCCs). Both promote cancer progression and metastasis development, but while the former induces the loss of E-cadherin expression and, hence cadherin switching; the latter produces hematic blood vessel neo-formation and contribute to OSCC cell growth, tumor mass development, and dissemination. Cyclooxygenase-2 (COX-2) has an important role, not only in angiogenic mechanisms, but also in favoring cancer invasion. Indeed it decreases the expression of E-cadherin and leads to phenotypic changes in epithelial cells (EMT) enhancing their carcinogenic potential. Our aim is to evaluate the interplay between E-cadherin cytoplasmic delocalization, COX-2 up-regulation and COX-2 induced neo-angiogenesis in 120 cases of OSCC. We have analyzed the distribution and the number of neo-formed endothelial buds surrounding infiltrating cells that express COX-2, as well as the neo-formed vessels in chronic inflammatory infiltrate, which surround the tumor. A double immunostaining method was employed in order to verify co-localization of endothelial cell marker (CD34) and COX-2. IHC has also been used to assess E-cadherin expression. Our data demonstrate that the OSCC cells, which lose membranous E-cadherin staining, acquiring a cytoplasmic delocalization, overexpress COX-2. Moreover, we find a new CD34+ vessel formation (sprouting angiogenesis). Only basaloid type of OSCC showes low level of COX-2 expression together with very low level of neo-angiogenesis and consequent tumor necrosis. The well-known anti-metastatic effect of certain COX-2 inhibitors suggests that these molecules might have clinical utility in the management of advanced cancers.

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The Role of E-Cadherin Down-Regulation in Oral Cancer: CDH1 Gene Expression and Epigenetic Blockage

Cited by 53 publications

References 31 publications

ITRAQ-Based Proteomics Analysis of Triptolide On Human A549 Lung Adenocarcinoma Cells

ITRAQ-Based Proteomics Analysis of Triptolide On Human A549 Lung Adenocarcinoma Cells

Expression of cancer stem cell biomarkers as a tool for a correct therapeutic approach to hepatocellular carcinoma

Expression and clinical implication of cyclooxygenase-2 and E-cadherin in oral squamous cell carcinomas

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