Enhancement of in vitro cell motility and invasiveness of human malignant pleural mesothelioma cells through the HIF-1α-MUC1 pathway

Goudarzi, Houman; Iizasa, Hisashi; Furuhashi, Masako; Nakazawa, Seitaro; Nakane, Rie; Liang, Shangdong; Hida, Kyoko; Yanagihara, Kazuyoshi; Kubo, Takanori; Nakagawa, Koji; Kobayashi, Masanobu; Irimura, Tatsuro; Hamada, Junichi

doi:10.1016/j.canlet.2013.07.020

Cited by 8 publications

(6 citation statements)

References 46 publications

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“…Similar to the previous study [ 40 ], hypoxia enhanced the migratory and invasive properties in HMM cells. Additionally, the present study showed that hypoxia promoted EMT process in HMM cells.…”

Section: Discussionsupporting

confidence: 89%

Hypoxia promotes acquisition of aggressive phenotypes in human malignant mesothelioma

et al. 2018

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BackgroundHypoxia is a hallmark of the solid tumor microenvironment and is associated with poor outcomes in cancer patients. The present study was performed to investigate mechanisms underlying the hypoxia-induced phenotypic changes using human malignant mesothelioma (HMM) cells.MethodsHypoxic conditions were achieved by incubating HMM cells in the air chamber. The effect of hypoxia on phenotype changes in HMM cells was investigated by performing in vitro clonogenicity, drug resistance, migration, and invasion assays. Signaling pathways and molecules involved in the more aggressive behaviors of HMM cells under hypoxia were investigated. A two-tailed unpaired Student’s t-test or one-way ANOVA with Bonferroni post-test correction was used in this study.ResultsHypoxic conditions upregulated hypoxia-inducible factor 1 alpha (HIF-1α) and HIF-2α in parallel with the upregulation of its target, Glut-1, in HMM cells. In vitro clonogenicity of HMM cells was significantly increased in hypoxic conditions, but the proliferation of cells at a high density in hypoxia was lower than that in normoxic conditions. The expression levels of HIF-2α and Oct4 were increased in hypoxic HMM cells. The percentage of cells with high CD44 expression was significantly higher in HMM cells cultured in hypoxia than those cultured in normoxia. Hypoxia significantly enhanced the resistance of HMM cells to cisplatin, which occurred through cytoprotection against cisplatin-induced apoptosis. While cisplatin treatment decreased the ratio of Bcl-2 to Bax in normoxic condition, hypoxia conversely increased the ratio in HMM cells treated with cisplatin. Hypoxia increased the mobility and invasiveness of HMM cells. Epithelial to mesenchymal transition was promoted, which was indicated by the repression of E-cadherin and the concomitant increase of vimentin in HMM cells.ConclusionsThe data illustrated that hypoxic conditions augmented the aggressive phenotypes of HMM cells at the biological and molecular levels. The present study provides valuable background information beginning to understand aggressiveness of HMM in tumor microenvironments, suggesting that a control measure for tumor hypoxia may be an effective therapeutic strategy to reduce the aggressiveness of cancer cells in HMM patients.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4720-z) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 89%

Hypoxia promotes acquisition of aggressive phenotypes in human malignant mesothelioma

et al. 2018

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“…Other evidences showed how miR-151-5p overexpression is linked with energy metabolism derangement and suggested a link with hypoxia 51 . This could explain their association with the overall survival that we observed here, since their high expression could promote the hypoxic microenvironment very well known to activate many signalling pathways involved in tumour initiation, progression and maintenance of MPM 52, 53 .…”

Section: Discussionmentioning

confidence: 53%

Deregulation of miRNAs in malignant pleural mesothelioma is associated with prognosis and suggests an alteration of cell metabolism

Santi

Melaiu

Bonotti

et al. 2017

Sci Rep

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Malignant pleural mesothelioma (MPM) is an aggressive human cancer and miRNAs can play a key role for this disease. In order to broaden the knowledge in this field, the miRNA expression was investigated in a large series of MPM to discover new pathways helpful in diagnosis, prognosis and therapy. We employed nanoString nCounter system for miRNA profiling on 105 MPM samples and 10 healthy pleura. The analysis was followed by the validation of the most significantly deregulated miRNAs by RT-qPCR in an independent sample set. We identified 63 miRNAs deregulated in a statistically significant way. MiR-185, miR-197, and miR-299 were confirmed differentially expressed, after validation study. In addition, the results of the microarray analysis corroborated previous findings concerning miR-15b-5p, miR-126-3p, and miR-145-5p. Kaplan-Meier curves were used to explore the association between miRNA expression and overall survival (OS) and identified a 2-miRNA prognostic signature (Let-7c-5p and miR-151a-5p) related to hypoxia and energy metabolism respectively. In silico analyses with DIANA-microT-CDS highlighted 5 putative targets in common between two miRNAs. With the present work we showed that the pattern of miRNAs expression is highly deregulated in MPM and that a 2-miRNA signature can be a new useful tool for prognosis in MPM.

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“…After knocking down MUC1 expression, reductions in HIF-1α protein expression, glucose uptake, and lactate release were observed [71]. Another study demonstrated that MUC1 facilitated HIF-1α translocation into the nucleus to act as a transcription factor for genes responsible for PDAC proliferation and invasion [72]. Moreover, the colocalization of the HIF-1α protein and VEGF mRNA identified via immunohistochemical analysis suggested that HIF-1α mediates the transcription of VEGF to induce angiogenesis in PDAC [73].…”

Section: Glycolysis and The Microenvironment Hypoxic Microenvironmentmentioning

confidence: 99%

Glycometabolic rearrangements--aerobic glycolysis in pancreatic cancer: causes, characteristics and clinical applications

Cao

et al. 2020

J Exp Clin Cancer Res

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Pancreatic cancer is one of the most malignant tumors worldwide, and pancreatic ductal adenocarcinoma is the most common type. In pancreatic cancer, glycolysis is the primary way energy is produced to maintain the proliferation, invasion, migration, and metastasis of cancer cells, even under normoxia. However, the potential molecular mechanism is still unknown. From this perspective, this review mainly aimed to summarize the current reasonable interpretation of aerobic glycolysis in pancreatic cancer and some of the newest methods for the detection and treatment of pancreatic cancer. More specifically, we reported some biochemical parameters, such as newly developed enzymes and transporters, and further explored their potential as diagnostic biomarkers and therapeutic targets.

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Enhancement of in vitro cell motility and invasiveness of human malignant pleural mesothelioma cells through the HIF-1α-MUC1 pathway

Cited by 8 publications

References 46 publications

Hypoxia promotes acquisition of aggressive phenotypes in human malignant mesothelioma

Hypoxia promotes acquisition of aggressive phenotypes in human malignant mesothelioma

Deregulation of miRNAs in malignant pleural mesothelioma is associated with prognosis and suggests an alteration of cell metabolism

Glycometabolic rearrangements--aerobic glycolysis in pancreatic cancer: causes, characteristics and clinical applications

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