Immunohistochemical and molecular analysis of PI3K/<scp>AKT</scp>/m<scp>TOR</scp> pathway in esophageal carcinoma

Tasioudi, Konstantia E.; Sakellariou, Stratigoula; Levidou, Georgia; Theodorou, Dimitrios; Michalopoulos, Nikolaos V.; Patsouris, Efstratios; Korkolopoulou, Penelope; Saetta, Angelica A.

doi:10.1111/apm.12398

Cited by 21 publications

(15 citation statements)

References 37 publications

(62 reference statements)

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“…Loss of PTEN in prostate cancer is associated with tumor aggression and poor outcome. In fact, mutations that activate the PI3K (phosphatidylinositol-3-kinase)-mTOR pathway are frequently found in many cancers, including AIDS-related lymphomas [31], and esophageal cancer, as mentioned above [29,32,33,34]. PTEN is widely known as a tumor suppressor and a guardian of the genome [35].…”

Section: Resultsmentioning

confidence: 99%

Ribosomal DNA copy number loss and sequence variation in cancer

et al. 2017

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Ribosomal DNA is one of the most variable regions in the human genome with respect to copy number. Despite the importance of rDNA for cellular function, we know virtually nothing about what governs its copy number, stability, and sequence in the mammalian genome due to challenges associated with mapping and analysis. We applied computational and droplet digital PCR approaches to measure rDNA copy number in normal and cancer states in human and mouse genomes. We find that copy number and sequence can change in cancer genomes. Counterintuitively, human cancer genomes show a loss of copies, accompanied by global copy number co-variation. The sequence can also be more variable in the cancer genome. Cancer genomes with lower copies have mutational evidence of mTOR hyperactivity. The PTEN phosphatase is a tumor suppressor that is critical for genome stability and a negative regulator of the mTOR kinase pathway. Surprisingly, but consistent with the human cancer genomes, hematopoietic cancer stem cells from a Pten-/- mouse model for leukemia have lower rDNA copy number than normal tissue, despite increased proliferation, rRNA production, and protein synthesis. Loss of copies occurs early and is associated with hypersensitivity to DNA damage. Therefore, copy loss is a recurrent feature in cancers associated with mTOR activation. Ribosomal DNA copy number may be a simple and useful indicator of whether a cancer will be sensitive to DNA damaging treatments.

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Section: Resultsmentioning

confidence: 99%

Ribosomal DNA copy number loss and sequence variation in cancer

et al. 2017

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“…VEGF signaling has been demonstrated to play a critical role in the growth and metastasis of multiple cancers [33]. Furthermore, the PI3K/Akt/mTOR signaling pathway can promote cell apoptosis and decrease cell proliferation by reducing Plk1 and could be a potential therapeutic target [34]. In the PPI network, we found three high-degree proteins encoded by the target genes MAPK1, RB1, and CLTC, which play key roles in a variety of tumors.…”

Section: Discussionmentioning

confidence: 90%

A Novel Three-miRNA Signature Identified Using Bioinformatics Predicts Survival in Esophageal Carcinoma

Zhang

Dai

2020

BioMed Research International

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Objective. We identified differentially expressed microRNAs (DEMs) between esophageal carcinoma (ESCA) tissues and normal esophageal tissues. We then constructed a novel three-miRNA signature to predict the prognosis of ESCA patients using bioinformatics analysis. Materials and Methods. We combined two microarray profiling datasets from the Gene Expression Omnibus (GEO) database and RNA-seq datasets from the Cancer Genome Atlas (TCGA) database to analyze DEMs in ESCA. The clinical data from 168 ESCA patients were selected from the TCGA database to assess the prognostic role of the DEMs. The TargetScan, miRDB, miRWalk, and DIANA websites were used to predict the miRNA target genes. Functional enrichment analysis was conducted using the Database for Annotation, Visualization, and Integrated Discovery (David), and protein-protein interaction (PPI) networks were obtained using the Search Tool for the Retrieval of Interacting Genes database (STRING). Results. With cut-off criteria of P<0.05 and |log2FC| > 1.0, 33 overlapping DEMs, including 27 upregulated and 6 downregulated miRNAs, were identified from GEO microarray datasets and TCGA RNA-seq count datasets. The Kaplan–Meier survival analysis indicated that a three-miRNA signature (miR-1301-3p, miR-431-5p, and miR-769-5p) was significantly associated with the overall survival of ESCA patients. The results of univariate and multivariate Cox regression analysis showed that the three-miRNA signature was a potential prognostic factor in ESCA. Furthermore, the gene functional enrichment analysis revealed that the target genes of the three miRNAs participate in various cancer-related pathways, including viral carcinogenesis, forkhead box O (FoxO), vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (ErbB2), and mammalian target of rapamycin (mTOR) signaling pathways. In the PPI network, three target genes (MAPK1, RB1, and CLTC) with a high degree of connectivity were selected as hub genes. Conclusions. Our results revealed that a three-miRNA signature (miR-1301-3p, miR-431-5p, and miR-769-5p) is a potential novel prognostic biomarker for ESCA.

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“…mTOR can oversee multiple physiologic and disease processes such as cellular metabolism (69, 70), bone formation (71-73), diabetes (35, 43, 74-77), neurodegenerative disorders (37, 78-83), dementia (12, 84-86), and cancer (25, 27, 87-91). In addition, mTOR has a significant role in the modulation of autophagy induction (92).…”

Section: Circadian Rhythm Mtor and Sirt1mentioning

confidence: 99%

Moving to the Rhythm with Clock (Circadian) Genes, Autophagy, mTOR, and SIRT1 in Degenerative Disease and Cancer

Maiese¹

2017

CNR

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Background The mammalian circadian clock and its associated clock genes are increasingly be recognized as critical components for a number of physiological and disease processes that extend beyond hormone release, thermal regulation, and sleep-wake cycles. New evidence suggests that clinical behavior disruptions that involve prolonged shift work and even space travel may negatively impact circadian rhythm and lead to multi-system disease. Methods In light of the significant role circadian rhythm can hold over the body's normal physiology as well as disease processes, we examined and discussed the impact circadian rhythm and clock genes hold over lifespan, neurodegenerative disorders, and tumorigenesis. Results In experimental models, lifespan is significantly reduced with the introduction of arrhythmic mutants and leads to an increase in oxidative stress exposure. Interestingly, patients with Alzheimer's disease and Parkinson's disease may suffer disease onset or progression as a result of alterations in the DNA methylation of clock genes as well as prolonged pharmacological treatment for these disorders that may lead to impairment of circadian rhythm function. Tumorigenesis also can occur with the loss of a maintained circadian rhythm and lead to an increased risk for nasopharyngeal carcinoma, breast cancer, and metastatic colorectal cancer. Interestingly, the circadian clock system relies upon the regulation of the critical pathways of autophagy, the mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), and silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) as well as proliferative mechanisms that involve the wingless pathway of Wnt/β-catenin pathway to foster cell survival during injury and block tumor cell growth. Conclusions Future targeting of the pathways of autophagy, mTOR, SIRT1, and Wnt that control mammalian circadian rhythm may hold the key for the development of novel and effective therapies against aging- related disorders, neurodegenerative disease, and tumorigenesis.

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Immunohistochemical and molecular analysis of PI3K/AKT/mTOR pathway in esophageal carcinoma

Cited by 21 publications

References 37 publications

Ribosomal DNA copy number loss and sequence variation in cancer

Ribosomal DNA copy number loss and sequence variation in cancer

A Novel Three-miRNA Signature Identified Using Bioinformatics Predicts Survival in Esophageal Carcinoma

Moving to the Rhythm with Clock (Circadian) Genes, Autophagy, mTOR, and SIRT1 in Degenerative Disease and Cancer

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