Wild-type phosphatase and tensin homolog deleted on chromosome 10 improved the sensitivity of cells to rapamycin through regulating phosphorylation of Akt in esophageal squamous cell carcinoma

2016 ◽  
pp. n/a-n/a ◽  
Author(s):  
Z. Lu ◽  
J. Wang ◽  
Y. Zheng ◽  
S. Yang ◽  
M. Liu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Wild Type ◽  
Chromosome 10 ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog

PS02.024: PRIMA-1 INDUCES P53-MEDIATED APOPTOSIS BY UPREGULATING NOXA IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA WITH TP53 MISSENSE MUTATION

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 126-127
Author(s):  
Haruna Furukawa ◽  
Tomoki Makino ◽  
Makoto Yamasaki ◽  
Koji Tanaka ◽  
Yasuhiro Miyazaki ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Missense Mutation ◽  
Cell Lines ◽  
Squamous Cell ◽  
Antitumor Effect ◽  
Xenograft Model ◽  
Wild Type ◽  
Massive Apoptosis

Abstract Background TP53 is associated with the resistance of cytotoxic treatment and patient prognosis, and the mutation rate of TP53 in esophageal squamous cell carcinoma (ESCC) is extraordinarily high, at over 90%. PRIMA-1 (p53 re-activation and induction of massive apoptosis) has recently been reported to restore wild type activity to mutant p53 and induce massive p53-dependent apoptosis. APR-246 (methylated PRIMA-1) has been tested in a phase I/II clinical trial with promising results; however, the effects and mechanism in ESCC remain unknown. This study was designed to assess the antitumor effect of PRIMA-1 treatment in both ESCC cell lines with different TP53 status and an ESCC xenograft model and uncover the molecular mechanism of PRIMA-1. Methods After evaluating the TP53 mutation status of a panel of eleven ESCC cell lines by Sanger sequencing, we assessed the in vitro effect of PRIMA-1 administration on cells with different p53 status by conducting cell viability and apoptosis assays. The expression levels of proteins in TP53-related pathways were examined by Western blotting, while knockdown studies were conducted to investigate the mechanism underlying PRIMA-1’s function. An ESCC xenograft model was further used to evaluate the therapeutic effect of PRIMA-1 in vivo. Results PRIMA-1 markedly inhibited cell growth and induced apoptosis by upregulating Noxa expression in ESCC cell lines with a TP53 missense mutation, whereas no apoptosis was induced in ESCC with wild type TP53 and with TP53 frameshift and nonsense mutations. Importantly, the knockdown of Noxa cancelled the apoptosis induced by PRIMA treatment in ESCC cell lines with a TP53 missense mutation. PRIMA-1 administration, compared with placebo, showed a significant antitumor effect by inducing Noxa in the xenograft model of an ESCC cell line with a TP53 missense mutation. Conclusion PRIMA-1 exhibits a significant antitumor effect, inducing massive apoptosis through the upregulation of Noxa in ESCC with a TP53 missense mutation. Disclosure All authors have declared no conflicts of interest.

Anterior gradient 2 regulates cancer progression in TP53‑wild‑type esophageal squamous cell carcinoma

2021 ◽  
Vol 46 (6) ◽  
Author(s):  
Kazuya Takabatake ◽  
Hirotaka Konishi ◽  
Tomohiro Arita ◽  
Satoshi Kataoka ◽  
Jun Shibamoto ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Progression ◽  
Squamous Cell ◽  
Wild Type

scholarly journals Exploration of Potential Roles of a New LOXL2 Splicing Variant Using Network Knowledge in Esophageal Squamous Cell Carcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Bing-Li Wu ◽  
Guo-Qing Lv ◽  
Hai-Ying Zou ◽  
Ze-Peng Du ◽  
Jian-Yi Wu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Splice Variant ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Splice Variants ◽  
Lysyl Oxidase ◽  
Wild Type

LOXL2 (lysyl oxidase-like 2), an enzyme that catalyzes oxidative deamination of lysine residue, is upregulated in esophageal squamous cell carcinoma (ESCC). A LOXL2 splice variant LOXL2-e13 and its wild type were overexpressed in ESCC cells followed by microarray analyses. In this study, we explored the potential role and molecular mechanism of LOXL2-e13 based on known protein-protein interactions (PPIs), following microarray analysis of KYSE150 ESCC cells overexpressing a LOXL2 splice variant, denoted by LOXL2-e13, or its wild-type counterpart. The differentially expressed genes (DEGs) of LOXL2-WT and LOXL2-e13 were applied to generate individual PPI subnetworks in which hundreds of DEGs interacted with thousands of other proteins. These two DEG groups were annotated by Functional Annotation Chart analysis in the DAVID bioinformatics database and compared. These results found many specific annotations indicating the potential specific role or mechanism for LOXL2-e13. The DEGs of LOXL2-e13, comparing to its wild type, were prioritized by the Random Walk with Restart algorithm. Several tumor-related genes such as ERO1L, ITGA3, and MAPK8 were found closest to LOXL2-e13. These results provide helpful information for subsequent experimental identification of the specific biological roles and molecular mechanisms of LOXL2-e13. Our study also provides a work flow to identify potential roles of splice variants with large scale data.

scholarly journals CircCNTNAP3-TP53-positive feedback loop suppresses malignant progression of esophageal squamous cell carcinoma

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Hui Wang ◽  
Xuming Song ◽  
Yajing Wang ◽  
Xuewen Yin ◽  
Yingkuan Liang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Malignant Progression ◽  
Gene Transcript ◽  
Wild Type ◽  
Positive Feedback Loop

AbstractMutation or downregulation of p53 (encoded by TP53) accelerates tumorigenesis and malignant progression in esophageal squamous cell carcinoma (ESCC). However, it is still unknown whether circular RNAs (circRNAs), a novel class of endogenous noncoding RNAs, participate in the regulation of this progress. In this study, we explored the expression profiles of circRNAs in three paired samples of ESCC and identified cCNTNAP3, which is a circRNA that originates from the CNTNAP3 gene transcript and is highly expressed in normal human esophageal tissue. However, we found that the cCNTNAP3 expression level was significantly downregulated in ESCC tissues. In vitro and in vivo studies revealed that cCNTNAP3 inhibited proliferation and increased apoptosis in p53 wild-type ESCC cells, but not in mutant cells. Mechanistically, we found that cCNTNAP3 promotes the expression of p53 by sponging miR-513a-5p. Rescue assay confirmed that the suppressive function of cCNTNAP3 was dependent on miR-513a-5p. We also observed that p53/RBM25 participated in the formation of cCNTNAP3, which implied the existence of a positive feedback loop between cCNTNAP3 and p53. Furthermore, the downregulation of cCNTNAP3 was significantly correlated with later T stage and thus can serve as an independent risk factor for the overall survival of patients with p53 wild-type ESCC. In conclusion, the cCNTNAP3-TP53 positive feedback loop may provide a potential target for the management of ESCC, which also reveals the important role of circRNAs in the regulation of p53.

The genetic profiles of esophageal squamous cell carcinoma (ESCC) in Hebei, a northern province of China.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15558-e15558
Author(s):  
Jing Zuo ◽  
Yimeng Jia ◽  
Yudong Wang ◽  
Zhisong Fan ◽  
Long Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Notch Signaling Pathway ◽  
Wild Type ◽  
Single Nucleotide Variants ◽  
Genomic Alterations ◽  
Ccnd1 Amplification ◽  
Formalin Fixed Paraffin Embedded

e15558 Background: Esophageal squamous cell carcinoma (ESCC) is a common malignancy without effective therapy. Methods: DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) sections from 29 ESCC samples. A panel of 520 genes was sequenced with NGS to identify genomic alterations at an average sequencing depth of 1000×. Results: In total, 421 genomic alterations were identified. We identified 230 single nucleotide variants (SNVs) and 35 insertions and deletions (indels) , 147 CNAs, 9 deletions and 0 translocations. The most frequently mutated genes were TP53 (97%), NOTCH1 (31%), CDKN2A (21%), NFKBIA (21%). Most frequent CN gains were observed in FGF3/4/19/CCND1(41%) which were co-occurrence in cBioPortal.By performing targeted NGS in 29 ESCC samples, we found a median TMB of 5.6/Mb (range: 0.8 to 42.9/Mb).TMB-high was located according to TMB > = 10, where 17.2% of the samples were TMB-H.C·G > T·A transversions were the most common mutations, followed by G·C > A·T transitions,The patients with NFKBIA mutation were all significantly older (p = 0.05), and the patients with FGF3/4/19/CCND1 amplification were mostly moderately differentiated, and the patients without high differentiation, suggesting a higher degree of malignancy (p = 0.03). CDKN2A, FGF3/4/19/CCND1 amplification, and NFKBIA mutated were associated with a smaller invasion depth, respectively (p = 0,p = 0.03,p = 0.05). Patients with wild type KMT2D had earlier stage, and all N0 stages were wild type for KMT2D (p = 0.03).Notably, high activity of DNA damage,Cell cycle and Notch signaling pathway might be particularly promising strategies for ESCC.In potential therapeutic target analysis, CDKN2A(20.7%) and PIK3CA (13.8%) were the validated and candidate therapeutic targeted genes. Conclusions: Collectively, our data provide comprehensive insights into the mutational signatures of ESCC and identify markers for early diagnosis and potential therapeutic targets.

scholarly journals Immunohistochemical expression of phosphatase and tensin homolog in histologic gradings of oral squamous cell carcinoma

2016 ◽  
Vol 7 (4) ◽  
pp. 524 ◽  
Author(s):  
ShinyS.R. Jasphin ◽  
Dinkar Desai ◽  
Siddharth Pandit ◽  
NithinM Gonsalves ◽  
PreethiB Nayak ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Immunohistochemical Expression ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog

Wnt 1 activates TCF/LEF transcription in esophageal squamous cell carcinoma

2001 ◽  
Vol 120 (5) ◽  
pp. A45-A46
Author(s):  
T MIZUSHIMA ◽  
H NAKAGAWA ◽  
A RUSTGI
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell
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