Esophageal 3D organoids of MPV17-/- mouse model of mitochondrial DNA depletion show epithelial cell plasticity and telomere attrition.

Esophageal 3D organoids of MPV17-/- mouse model of mitochondrial DNA depletion show epithelial cell plasticity and telomere attrition. Oncotarget. 2019 Oct 22;10(58):6245-6259 Authors: Guha M, Srinivasan S, Sheehan MM, Kijima T, Ruthel G, Whelan K, Tanaka K, Klein-Szanto A, Chandramouleeswaran PM, Nakagawa H, Avadhani NG Abstract Esophageal squamous cell carcinoma (ESCC) is an aggressive cancer with late-stage detection and poor prognosis. This emphasizes the need to identify new markers for early diagnosis and treatment. Altered mitochondrial genome (mtDNA) content in primary tumors correlates with poor patient prognosis. Here we used three-dimensional (3D) organoids of esophageal epithelial cells (EECs) from the MPV17-/- mouse model of mtDNA depletion to investigate the contribution of reduced mtDNA content in ESCC oncogenicity. To test if mtDNA defects are a contributing factor in ESCC, we used oncogenic stimuli such as ESCC carcinogen 4-nitroquinoline oxide (4-NQO) treatment, or expressing p53R175H oncogenic driver mutation. We observed that EECs and 3D-organoids with mtDNA depletion had cellular, morphological and genetic alterations typical of an oncogenic transition. Furthermore, mitochondrial dysfunction induced cellular transformation is accompanied by elevated mitochondrial fission protein, DRP1 and pharmacologic inhibition of mitochondrial fission by mDivi-1 in the MPV17-/- organoids reversed the phenotype to that of normal EEC organoids. Our s...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research

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Conclusions: Taken together, our study identified a novel role and mechanism of EP300 in ESCC and provided epigenetic therapeutic strategies for the treatment of ESCC.
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
Abstract BACKGROUND: Rad51 is a protein which plays a vital role in DNA double-strand break repair and maintenance of telomeres. However, the underlying mechanism for its action in esophageal squamous cell carcinoma (ESCC) remains unclear. PATIENTS AND METHODS: Eighty-seven patients with ESCC were enrolled in this study. Expression of Rad51 in ESCC was determined by immunohistochemistry and correlated with clinicopathological variables by Chi square test. The role of Rad51 in patient survival was determined by Kaplan-Meier estimates. The effects of Rad51 knockdown and overexpression on esophageal cancer growt...
Source: Ann Oncol - Category: Cancer & Oncology Authors: Tags: Ann Surg Oncol Source Type: research
In conclusion, our study suggests that IBSP may be a valuable prognostic marker for ESCC patients.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In this study, four pairs of ESCC tissues were used for mRNA sequencing to determine differentially expressed genes (DEGs). 347 genes were found to be upregulated whereas 255 genes downregulated. By screening DEGs plus bioinformatics analyses such as KEGG, PPI and IPA, we found that there were independent interactions between KRT family members. KRT17 upregulation was confirmed in ESCC and its relationship with clinicopathological features were analysed. KRT17 was significantly associated with ESCC histological grade, lymph node and distant metastasis, TNM stage and five-year survival rate. Upregulation of KRT17 promoted E...
Source: Journal of Proteomics - Category: Biochemistry Authors: Tags: J Proteomics Source Type: research
Source: Cancer Management and Research - Category: Cancer & Oncology Tags: Cancer Management and Research Source Type: research
Esophageal cancer is a common human malignant tumor with high mortality. Glandular epithelial markers, such as CAM5.2, can be expressed in esophageal squamous cell carcinoma (ESCC), but the clinical significance of these cells in ESCC remains elusive. Immunohistochemical analysis of CAM5.2 was performed on 604 ESCC specimens using tissue microarray. Our study design and study population used retrospective cohorts based on the hospital information system and pathological information management system which included medical information, date of admission, procedures undergone, registration, examinations, and medication. In...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Observational Study Source Type: research
ConclusionThis strategy provides the means to generate tumor-reactive TCR-Ts for ESCC, which is especially important for patients without prior knowledge of specific epitopes and might be applied for other cancers.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
Authors: Hao J, Li S, Li J, Jiang Z, Ghaffar M, Wang M, Jia R, Chen S, Wang Y, Zeng Y Abstract Esophageal carcinoma (EC) is the sixth most deadly of all cancers. It is among the most malignant cancers due to its highly aggressive nature and low survival rate. The incidence of EC is high in Asia, particularly in Southern areas including China, Iran and Japan. There is a large body of evidence to suggest an association between the melanoma antigen gene (MAGE) family and the initiation of cancer; however, there is no clear evidence to suggest an association between EC and MAGE. Discovery of the chemical and physiologi...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
CONCLUSIONS: MiR-148a inhibited the proliferation and invasion through directly targeting to MAP3K9 by ERK/MAPK pathway and EMT in ESCC cells. The newly identified miR-148a/MAP3K9 axis provides a novel insight into the pathogenesis of the esophagus squamous cell carcinoma. PMID: 31378889 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research
Publication date: 1 September 2019Source: Life Sciences, Volume 232Author(s): Fangfang Li, Zhen Zhang, Peng Wang, Penghao Wen, Quanxiao Xu, Yunlong Wang, Ping Pan, Lei MaAbstractAimsAmplified in liver cancer 1 gene (ALC1), a recently identified oncogene, was reported to be overexpressed in esophageal cancer cell lines and identified as a target oncogene in esophageal cancer pathogenesis. However, little literature is available to illustrate its significance in cisplatin resistance of esophageal squamous cell carcinoma (ESCC) cells. The aim of the current study was to investigate the effect of ALC1 on cisplatin cytotoxicity...
Source: Life Sciences - Category: Biology Source Type: research
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