scholarly journals CEP55 Positively Affects Tumorigenesis of Esophageal Squamous Cell Carcinoma and Is Correlated with Poor Prognosis

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Shu-Mei Yan ◽  
Lili Liu ◽  
Wan-Yi Gu ◽  
Li-Yun Huang ◽  
Yi Yang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Protein Expression ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Colony Formation ◽  
Disease Free Survival ◽  
Prognostic Indicator ◽  
Mrna And Protein Expression ◽  
And Migration

Centrosomal protein 55 (CEP55) is a centrosome- and midbody-associated protein that is overexpressed in several cancers. However, the underlying molecular mechanism of CEP55-mediated progression and metastasis of esophageal squamous cell carcinoma (ESCC) is not clear. In the current study, we detected CEP55 mRNA by qRT-PCR while protein expression was detected by western blot analysis and immunohistochemistry (IHC). In addition, we knocked down CEP55 and investigated the ability of CEP55 to affect colony formation and migration. Here, we report that CEP55 mRNA and protein expression was significantly increased in ESCC. IHC staining showed that CEP55 expression correlated with TNM stage ( p = 0.046 ) and lymph node metastases ( p = 0.024 ). According to overall survival (OS) and disease-free survival (DFS), patients whose tumors expressed a higher level of CEP55 had a poorer prognosis than those with low expression level of CEP55. A multivariate analysis revealed that CEP55 expression was an independent prognostic indicator for patients with ESCC. Knockdown of CEP55 decreased the colony formation ability and migration of ESCC cells and also reduced the phosphorylation of Src, FAK, and ERK. Therefore, our study implied that CEP55 may be a valuable biomarker and a potential target in the treatment of patients with ESCC.

PS02.051: HMGB IS INVOLVED IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA PROGRESSION

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 134-135
Author(s):  
Daiki Matsubara ◽  
Hirotaka Konishi ◽  
Katsutoshi Shoda ◽  
Tomohiro Arita ◽  
Toshiyuki Kosuga ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Protein Expression ◽  
Healthy Volunteers ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Plasma Samples ◽  
Tissue Samples ◽  
Mrna And Protein Expression

Abstract Background High-mobility group box-1 (HMGB1), originally characterized as a non-histone, nuclear DNA-binding protein, acts as a crucial proinflammatory cytokine, mediating a broad range of inflammatory responses as a secretory form. Recently, it has been reported to be involved in the tumorigenesis and progression of various types of malignancies, but it is unclear whether HMGB1 plays an important role in the progression of esophageal squamous cell carcinoma (ESCC). The aim of this study was to investigate the significance of HMGB1 in ESCC. Methods The tissue and plasma samples were obtained from ESCC patients at before or after operative period and healthy volunteers. The ESCC cell lines and normal human cell lines, such as fibroblast (WI-38) or Human umbilical vein endothelial cell (HUVEC), were used in vitro analyses. The expression levels of HMGB1 in tissue samples were measured by quantitative RT-PCR. The protein levels of HMGB1 were measured using the HMGB1 enzyme-linked immunosorbent assay kit in plasma samples, and using immunohistochemical staining or western blotting in tissue samples or cell lines. The functions of HMGB1 on the ESCC cell lines were investigated by proliferation, invasion, or migration assays. Results The mRNA and protein expression of HMGB1 in ESCC tissue was significantly higher than that in paired non-cancerous esophageal mucosa tissue. Plasma HMGB1 level was slightly higher, but not significant, in ESCC patients than in healthy volunteers. However, it was significantly higher in ESCC patients with Neoadjuvant chemotherapy (NAC) than in those without NAC. The mRNA and protein expression of HMGB1 were higher in ESCC cell lines than in WI-38 or HUVEC. In ESCC cells with high HMGB1 expression, knockdown of HMGB1 using specific siRNAs inhibited the cell proliferation, migration and invasion. Conclusion These findings suggest that HMGB1 plays a crucial role in tumor malignant potential through its overexpression in esophageal squamous cell carcinoma. Disclosure All authors have declared no conflicts of interest.

scholarly journals FLVCR1 Predicts Poor Prognosis and Promotes Malignant Phenotype in Esophageal Squamous Cell Carcinoma via Upregulating CSE1L

2021 ◽  
Vol 11 ◽  
Author(s):  
Suna Zhou ◽  
Mingxin Zhang ◽  
Chao Zhou ◽  
Yinnan Meng ◽  
Haihua Yang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Colony Formation ◽  
Xenograft Model ◽  
Migration And Invasion ◽  
Node Metastasis ◽  
And Migration

ObjectiveDysregulation of feline leukemia virus subgroup C receptor 1(FLVCR1) expression has been investigated in several tumors. However, the expression and role of FLVCR1 in esophageal squamous cell carcinoma (ESCC) remain largely unknown.MethodsFLVCR1 expression in tissues was measured by immunohistochemical staining (IHC). Celigo assay, MTT assay, colony formation, caspase 3/7 activity analysis, wound healing assay, Transwell migration, and invasion assay were applied to assess the effects of FLVCR1 on ESCC tumorigenesis. Coimmunoprecipitation (Co-IP) and liquid chromatography-mass spectrometry (LC-MS) were used to identify protein interactions with FLVCR1. An in vivo imaging system (IVIS) was used to investigate the functions of FLVCR1 on the growth and metastatic capability of ESCC cells in a xenograft model and a tail vein metastasis model.ResultsElevated expression of FLVCR1 was detected in ESCC tissues and predicted poor survival. Upregulated FLVCR1 was positively correlated with lymph node metastasis (N stage) and late tumor-node-metastasis (TNM) stage. FLVCR1 knockdown inhibited cell proliferation and colony formation ability, induced cell apoptosis, and repressed cell migration and invasion of ESCC in vitro. Inhibition of FLVCR1 markedly repressed tumorigenicity and metastasis of ESCC cells in vivo. Mechanistically, chromosome segregation 1–like (CSE1L) was identified to interact with FLVCR1 using a Co-IP assay. Moreover, the inhibitory effect of FLVCR1 knockdown on proliferation and migration was counteracted by the exogenous expression of CSE1L.ConclusionFLVCR1 plays a pivotal role in ESCC cell survival, growth, and migration. These functions may be partially dependent upon the protein interaction between FLVCR1 and CSE1L. In addition, FLVCR1 can be applied as a clinical prognostic marker for patients with ESCC.

MTA1 promotes tumorigenesis and development of esophageal squamous cell carcinoma via activating the MEK/ERK/p90RSK signaling pathway

2019 ◽  
Vol 41 (9) ◽  
pp. 1263-1272 ◽  
Author(s):  
Peng Nan ◽  
Ting Wang ◽  
Chunxiao Li ◽  
Hui Li ◽  
Jinsong Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Colony Formation ◽  
Cancer Proliferation ◽  
Invasion And Migration ◽  
And Migration

Abstract Metastasis-associated protein 1 (MTA1) is upregulated in multiple malignancies and promotes cancer proliferation and metastasis, but whether and how MTA1 promotes esophageal squamous cell carcinoma (ESCC) tumorigenesis remain unanswered. Here, we established an ESCC model in MTA1 transgenic mice induced by the chemical carcinogen 4-nitroquinoline 1-oxide (4-NQO) and found that MTA1 promotes ESCC tumorigenesis in mice. MTA1 overexpression was observed in ESCC cells and clinical ESCC samples. Overexpressed MTA1 increased colony formation and the invasiveness and migration of ESCC cells, whereas knock down of MTA1 in ESCC cells significantly decreased colony formation, invasion and migration in vitro and inhibited the growth of xenograft tumors in vivo. RNA sequencing (RNA-seq) analysis combined with western blot assays revealed that MTA1 promotes carcinogenesis by enhancing MEK/ERK/p90RSK signaling. The phosphorylation of MEK, ERK and their downstream target p90RSK was significantly decreased after MTA1 knockdown in ESCC cells and was increased in MTA1-overexpressing cells. Moreover, colony formation, invasion and migration potential were dramatically suppressed when cells overexpressing MTA1 were treated with MEK (PD0325901) or ERK (SCH772948) inhibitors. In conclusion, MTA1 plays a pivotal oncogenic role in ESCC tumorigenesis and development through activating the MEK/ERK/p90RSK pathway.

miR-375 inhibits the proliferation, migration and invasion of esophageal squamous cell carcinoma by targeting XPR1

2020 ◽  
Vol 20 ◽  
Author(s):  
Wenbin Wu ◽  
Yangmei Zhang ◽  
Xiaowu Li ◽  
Xiang Wang ◽  
Yuan Yuan
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Promoting Effect ◽  
Dual Luciferase Assay ◽  
Invasion And Migration ◽  
And Migration

Objective: The purpose of this study was to explore the mechanism of the miR-375/XPR1 axis in esophageal squamous cell carcinoma (ESCC) and provide a new idea for targeted therapy of ESCC. Methods: Differentially expressed genes in GEO and TCGA databases were analyzed by bioinformatics. The expression levels of miR-375 and XPR1 mRNA were detected by qRT-PCR. Protein expression of XPR1 was detected by western blot. Bioinformatics analysis and dual luciferase assay were conducted to confirm the targeting relationship between miR-375 and XPR1. The viability, proliferation, migration and invasion of cells in each treatment group were detected by CCK-8, colony formation, wound healing and Transwell assays. Results: Significantly down-regulated miR-375 and remarkably up-regulated XPR1 were observed in ESCC tissue and cells. Overexpression of miR-375 inhibited proliferation, invasion and migration of ESCC cells, and greatly reduced the promoting effect of XPR1 overexpression on cell proliferation, migration and invasion. Dual luciferase assay confirmed that miR-375 targeted and inhibited XPR1 expression in ESCC. Conclusion: These results demonstrate the regulatory role of the miR-375/XPR1 axis in ESCC cells and provide a new potential target for the precise treatment of patients with ESCC.

scholarly journals CALM1 promotes progression and dampens chemosensitivity to EGFR inhibitor in esophageal squamous cell carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tao Liu ◽  
Xiujuan Han ◽  
Shutao Zheng ◽  
Qing Liu ◽  
Aerziguli Tuerxun ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Prognostic Significance ◽  
Xenograft Model ◽  
Combined Effect ◽  
Egfr Inhibitor ◽  
Knock Out ◽  
And Migration

Abstract Background Calmodulin1 (CALM1) has been identified as one of the overexpression genes in a variety of cancers and EGFR inhibitor have been widely used in clinical treatment but it is unknown whether CALM1 and epidermal growth factor receptor (EGFR) have a synergistic effect in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to explore the synergistic effects of knock-out CALM1 combined with EGFR inhibitor (Afatinib) and to elucidate the role of CALM1 in sensitizing the resistance to Afatinib in ESCC. Method Immunohistochemistry (IHC) and qRT-PCR were used to examine the expression of CALM1 and EGFR in ESCC tissues. Kaplan–Meier survival analysis was used to analyze the clinical and prognostic significance of CALM1 and EGFR expression in ESCC. Furthermore, to evaluate the biological function of CALM1 in ESCC, the latest gene editing technique CRISPR/Cas9(Clustered regularly interspaced short palindromic repeats)was applied to knockout CALM1 in ESCC cell lines KYSE150, Eca109 and TE-1. MTT, flow cytometry, Transwell migration, scratch wound-healing and colony formation assays were performed to assay the combined effect of knock-out CALM1 and EGFR inhibitor on ESCC cell proliferation and migration. In addition, nude mice xenograft model was used to observe the synergistic inhibition of knock-out CALM1 and Afatinib. Results Both CALM1 and EGFR were found to be significantly over-expressed in ESCC compared with paired normal control. Over-expressed CALM1 and EGFR were significantly associated with clinical stage, T classification and poor overall prognosis, respectively. In vitro, the combined effect of knock-out CALM1 mediated by the lentivirus and EGFR inhibitor was shown to be capable of inhibiting the proliferation, inducing cell cycle arrest at G1/S stage and increasing apoptosis of KYSE-150 and Eca109 cells; invasion and migration were also suppressed. In vivo, the results of tumor weight and total fluorescence were markedly reduced compared with the sgCtrl-infected group and sgCAML1 group. Conclusion Our data demonstrated that knock-out of CALM1 could sensitize ESCC cells to EGFR inhibitor, and it may exert oncogenic role via promotion of EMT. Taken together, CALM1 may be a tempting target to overcome Afatinib resistance.

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