scholarly journals The regulation of acetylation and stability of HMGA2 via the HBXIP-activated Akt–PCAF pathway in promotion of esophageal squamous cell carcinoma growth

2020 ◽  
Vol 48 (9) ◽  
pp. 4858-4876 ◽  
Author(s):  
Yue Wu ◽  
Xue Wang ◽  
Feifei Xu ◽  
Lu Zhang ◽  
Tianjiao Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Binding Capacity ◽  
Disease Free Survival ◽  
Protein Accumulation ◽  
Advanced Tumor Stage ◽  
Advanced Tumor ◽  
Hmga2 Protein

Abstract High-mobility group AT-hook 2 (HMGA2) is an architectural transcription factor that plays essential roles in embryonic development and cancer progression. However, the mechanism of HMGA2 regulation remains largely uncharacterized. Here, we demonstrate that HMGA2 can be modulated by hepatitis B X-interacting protein (HBXIP), an oncogenic transcriptional coactivator, in esophageal squamous cell carcinoma (ESCC). HMGA2 expression was positively associated with HBXIP expression in clinical ESCC tissues, and their high levels were associated with advanced tumor stage and reduced overall and disease-free survival. We found that oncogenic HBXIP could posttranslationally upregulate HMGA2 protein level in ESCC cells. HBXIP induced HMGA2 acetylation at the lysine 26 (K26), resulting in HMGA2 protein accumulation. In this process, HBXIP increased the acetyltransferase p300/CBP-associated factor (PCAF) phosphorylation and activation via the Akt pathway, then PCAF directly interacted with HMGA2, leading to HMGA2 acetylation in the cells. HMGA2 K26 acetylation enhanced its DNA binding capacity and blocked its ubiquitination and then inhibited proteasome-dependent degradation. Functionally, HBXIP-stabilized HMGA2 could promote ESCC cell growth in vitro and in vivo. Strikingly, aspirin suppressed ESCC growth by inhibiting HBXIP and HMGA2. Collectively, our findings disclose a new mechanism for the posttranslational regulation of HMGA2 mediated by HBXIP in ESCC.

scholarly journals LncRNA GHET1 Promotes Esophageal Squamous Cell Carcinoma Cells Proliferation and Invasion via Induction of EMT

2017 ◽  
Vol 32 (4) ◽  
pp. 403-408 ◽  
Author(s):  
Hongfen Liu ◽  
Qiang Zhen ◽  
Yakun Fan
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Noncoding Rna ◽  
In Vitro Assays ◽  
Migration And Invasion ◽  
Advanced Tumor

Background Recent studies have shown that long noncoding RNA (IncRNA) gastric carcinoma highly expressed transcript 1 (GHET1) was involved in the progression of tumors. However, the role of GHET1 in esophageal squamous cell carcinoma (ESCC) remains unclear. Methods The expression of IncRNA GHET1 was examined in 55 paired ESCC tissues and adjacent nontumor tissues. Molecular and cellular techniques were used to explore the role of GHET1 on ESCC cells. Results Our data showed that GHET1 expression was significantly increased in ESCC tissues and cell lines. High GHET1 expression in ESCC tissues was significantly associated with poor differentiation, advanced tumor nodes metastasis stage, and lymph node metastasis. GHET1 showed high sensitivity and specificity for diagnosing ESCC. Our data from in vitro assays showed that GHET1 inhibition suppressed ESCC cells proliferation, migration, and invasion, and induced cells apoptosis. Furthermore, western blot showed that GHET1 inhibition significantly decreased the expression of vimentin and N-cadherin while it increased the expression of E-cadherin. Conclusions Our study indicates that GHET1 acts as an oncogene in ESCC and may represent a novel therapeutic target for the treatment of ESCC patients.

scholarly journals Abnormal p16 Expression and Prognostic Significance in Chinese Esophageal Squamous Cell Carcinoma

2020 ◽  
Author(s):  
Xue Zhang ◽  
Weijie Chen ◽  
Xiaolei Zhang ◽  
Lei Xu ◽  
Feng Gao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Negative Group ◽  
Expression Status ◽  
Focal Expression ◽  
P16 Expression

Abstract Background: The purpose of this study was to analysis p16 expression status and evaluate whether abnormal p16 expression was associated with prognosis in a large-scale Chinese esophageal squamous cell carcinoma (ESCC) patients. Methods: We retrospectively evaluated p16 expression status of 525 ESCC samples using immunohistochemistry. Associations between abnormal p16 expression and survival were analyzed. Results: P16 negative, focal expression and overexpression were found in 87.6%, 6.9% and 5.5% of ESCC patients. No significant association was observed between abnormal p16 expression and age, sex, tumor site and location, differentiation, vessel and nerve invasion, T stage and lymph node metastasis. In all patients, the survival of p16 focal expression group tended to be better compared with negative group (disease free survival/DFS P=0.040 and overall survival/OS P=0.052) and overexpression group (DFS P=0.201 and OS P=0.258), and there was no survival difference between negative group and overexpression group. The multivariate analysis for OS and DFS only found clinical stage was a significantly independent prognostic factor (P<0.001). When patients were divided into I-II stage (n=290) and III-IVa stage (n=235), the survival of focal expression group was better compared with negative group (DFS P=0.015 and OS P=0.019), tended to be better compared with overexpression group (DFS P=0.405 and OS P=0.432) in I-II stage ESCC, which was not found in III-IVa stage ESCC.Conclusion: P16 overexpression or negative tend to be associated with unfavorable outcomes, especially in I-II stage ESCC. Our study will help to identify a subgroup of ESCC patients with excellent prognosis after surgical therapy.

scholarly journals Galectin-1 Expression is Associated with the Response and Survival Following Preoperative Chemoradiotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3147
Author(s):  
Shau-Hsuan Li ◽  
Yen-Hao Chen ◽  
Hung-I Lu ◽  
Chien-Ming Lo ◽  
Chao-Cheng Huang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Surgical Margin ◽  
Disease Free Survival ◽  
Complete Response ◽  
Preoperative Chemoradiotherapy ◽  
Positive Surgical Margin

The galectin-1 has been found to be involved in poor outcomes after treatment of a variety of cancers. To the best of our knowledge, however, the significance of galectin-1 expression in the sensitivity to chemoradiotherapy (CCRT) of patients with locally advanced esophageal squamous cell carcinoma (ESCC) remains unclear. Expression levels of galectin-1 were evaluated by immunohistochemistry and correlated with the treatment outcome in 93 patients with locally advanced ESCC who received preoperative CCRT between 1999 and 2012. Galectin-1 expression was significantly associated with the pathological complete response (pCR). The pCR rates were 36.1% and 13.0% (p = 0.01) in patients with low and high galectin-1 expression, respectively. Univariate analyses revealed that galectin-1 overexpression, clinical 7th American Joint Committee on Cancer (AJCC) stage III and a positive surgical margin were significant factors of worse overall survival and disease-free survival. In multivariate analyses, galectin-1 overexpression and a positive surgical margin represented the independent adverse prognosticators. Therefore, galectin-1 expression both affects the pCR and survival in patients with locally advanced ESCC receiving preoperative CCRT. Our results suggest that galectin-1 may be a potentially therapeutic target for patients with ESCC treated with preoperative CCRT.

scholarly journals Loss of CADM1/TSLC1 Expression Is Associated with Poor Clinical Outcome in Patients with Esophageal Squamous Cell Carcinoma

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
De Zeng ◽  
Xiao Wu ◽  
Jin Zheng ◽  
Yixuan Zhuang ◽  
Jiongyu Chen ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cox Regression ◽  
Histological Grade ◽  
Disease Free Survival ◽  
Early Recurrence ◽  
Clinicopathological Parameters ◽  
Survival Duration

Aims. We sought to determine the relationship between CADM1/TSLC1 expression and clinicopathological characteristics in patients with esophageal squamous cell carcinoma (ESCC) and the correlation with survival.Materials and Methods. Two hundred and ninety-three ESCC tissues and paired adjacent normal esophageal tissues were immunohistochemically assessed in this study. The association of CADM1/TSLC1 with clinicopathological parameters, as well as disease-free survival (DFS) and overall survival (OS), was determined based on the Kaplan-Meier method and Cox regression models.Results. CADM1/TSLC1 was detected in 236 (80.5%) tumor tissues and 19 (8.0%) paired adjacent normal esophageal tissues. Decreased CADM1/TSLC1 expression was correlated with more advanced histological grade. CADM1/TSLC1 negative tumors were more frequently observed in male cases than in female cases. DFS and OS in the CADM1/TSLC1 negative group were significantly shorter than those in the positive group, particularly in male patients with ESCC.Conclusion. Loss or reduction of CADM1/TSLC1 expression is associated with more advanced histological grade and predicts early recurrence and short survival duration. Thus, loss of CADM1/TSLC1 could be a prognostic factor that can be used to assess the risk of recurrence and survival.

scholarly journals Screening and identification of significant genes in esophageal squamous cell carcinoma by bioinformatical analysis

2020 ◽  
Author(s):  
Weirui Ren ◽  
Chuang Zhang ◽  
Lei Pan ◽  
Weijing Wang ◽  
Wenjuan Zhao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Disease Free Survival ◽  
Hub Genes ◽  
Incidence And Mortality ◽  
Bioinformatical Analysis

Abstract Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers with notably high incidence and mortality rates. However, the molecular mechanism underlying ESCC pathogenesis and prognosis is very complicated. The main objective of our investigation has been to obtain some knowledge of significant genes with poor outcome and their underlying mechanisms.Methods: Gene expression profiles of GSE26886, GSE23400, GSE20347 and GSE17351 were available from GEO database. The differentially expressed genes (DEGs) were identified, and function enrichment analyses were performed. The protein-protein interaction network (PPI) was constructed and the module analysis was performed using STRING and Cytoscape software.Results: A total of 105 DEGs were identified between normal esophagus and ESCC bioinformatical analysis samples. Functional annotations of the common DEGs indicate that extracellular matrix (ECM) remodeling plays a key role in tumor formation and progression.18 hub genes were identified and disease free survival analysis showed that CDKN3, RAD51AP1, KIF4A may be involved in poor prognosis in ESCC patients.Conclusions: DEGs and hub genes identified in the present study help us understand the molecular mechanisms underlying the carcinogenesis and progression of ESCC, and provide candidate targets for diagnosis and treatment of ESCC.

scholarly journals Effect of Long Term Prediagnostic Aspirin Intake on the Prognosis of Esophageal Squamous Cell Carcinoma Receiving Radical Surgery

2021 ◽  
Author(s):  
Wenqiao Jia ◽  
Cong Wang ◽  
Ming Lu ◽  
Yufeng Cheng
Keyword(s):  
Squamous Cell Carcinoma ◽  
Survival Analysis ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Radical Surgery ◽  
Disease Free Survival ◽  
Ptnm Stage ◽  
Aspirin Group

Abstract Background:The effect of long term prediagnostic aspirin intake on the prognosis of esophageal squamous cell carcinoma (ESCC) is unclear. We aimed to reveal the effect of long term prediagnostic aspirin intake on survival of ESCC patients receiving radical surgery. Methods:147 eligible ESCC patients who received radical surgery for primary treatment were enrolled in this study. Patients who had used aspirin regularly for more than 3 months before diagnose were classified as aspirin group and patients who had never used aspirin before diagnose and surgery were served as non-aspirin group. The recurrence rate, disease-free survival (DFS) and overall survival (OS) were compared between the two groups to verify the effect of aspirin. Results:Patients were clarified into aspirin group (n=57) and non-aspirin group (n=90). The DFS and OS were both significantly shorter in aspirin group than non-aspirin group (DFS: 23.1±18.0 months vs. 30.9±19.8 months, P=0.018; OS: 29.8±17.4 months vs. 35.2±18.2 months, P=0.082). Survival analysis revealed that OS decreased in aspirin group than in non-aspirin group, however, it did not reach significance (P=0.074). DFS decreased significantly in aspirin group than non-aspirin group in both univariate (P=0.007) and multivariate (P=0.002) survival analysis. Subgroup analysis revealed that in pTNM stage 2, OS and DFS were reduced in non-aspirin group compared with aspirin group (P=0.048 and P=0.003, respectively), while no difference was found in stage 3.Conclusions:Long term prediagnostic aspirin intake may cause poor DFS in ESCC patients receiving radical surgery, especially for those in pTNM stage 2.

scholarly journals CD73 Promotes Tumor Progression in Patients with Esophageal Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3982
Author(s):  
Yen-Hao Chen ◽  
Hung-I Lu ◽  
Chien-Ming Lo ◽  
Shau-Hsuan Li
Keyword(s):  
Squamous Cell Carcinoma ◽  
Prognostic Factor ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Independent Prognostic Factor ◽  
Expression Levels ◽  
Invasion And Migration ◽  
Patient Responses

Cluster of differentiation (CD)-73 plays pivotal roles in the regulation of immune reactions via the production of extracellular adenosine, and the overexpression of CD73 is associated with worse outcomes in several types of cancers. Here, we identified 167 esophageal squamous cell carcinoma (ESCC) patients who underwent esophagectomy, including 64 and 103 patients with high and low expression levels of CD73, respectively. Univariate and multivariate analyses showed high expression of CD73 was an independent prognostic factor for worse disease-free survival and overall survival. In addition, we selected another cohort consisting of 38 ESCC patients receiving nivolumab or pembrolizumab and found that treatment response and survival benefit to immunotherapy were strongly correlated with the expression levels of CD73/programmed death ligand 1. Moreover, the transwell assay revealed knockdown of CD73 in two ESCC cell lines, TE1 and KYSE30, exhibited significantly reduced abilities of cell invasion and migration. CD73 silencing also showed that the protein expression levels of CD73, vimentin, and snail were downregulated, while those of E-cadherin were upregulated in Western blotting. The findings of our study indicate CD73 may be an independent prognostic factor for ESCC patients who underwent esophagectomy. Furthermore, it may be associated with the patient responses to immunotherapy.

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