Quantitative Proteomic Profiling of Pleomorphic Human Sarcoma Identifies CLIC1 as a Dominant Pro-Oncogenic Receptor Expressed in Diverse Sarcoma Types

Murray, Euan; Hernychová, Lenka; Ščigelová, Michaela; Ho, Jenny; Nekulova, Marta; O’Neill, J. Robert; Nenutil, Rudolf; Veselý, Karel; Dundas, Sinclair R.; Dhaliwal, Catharine; Henderson, Hannah; Hayward, Richard L; Salter, Donald; Vojtěšek, Bořivoj; Hupp, Ted R.

doi:10.1021/pr4010713

Cited by 12 publications

(10 citation statements)

References 63 publications

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“… 14 , 22 , 24 , 26 , 27 It was evaluated to be the most penetrating receptor among commonly dysregulated proteins within three sarcomas. 23 This protein plays an important role in the metastasis of colonic cancer. 24 In gliomas, CLIC1 expression is inversely related to patient survival.…”

Section: Discussionmentioning

confidence: 99%

Expression of CLIC1 as a potential biomarker for oral squamous cell carcinoma: a preliminary study

Xu¹,

Feng²,

Li³

et al. 2018

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PurposeCLIC1, a member of the highly conserved class ion-channel protein family, is frequently upregulated in multiple human malignancies and has been demonstrated to play a critical role in cell proliferation, apoptosis, and invasion. However, limited is known about its expression, biological functions, and action mechanism in oral malignancies. We aimed to evaluate whether CLIC1 could be a biomarker for oral squamous cell carcinoma (OSCC).MethodsImmunohistochemistry was used to analyze the expression of CLIC1 in tissue. CLIC1 protein and mRNA were measured through Western immunoblotting and quantitative real-time PCR. CLIC1 protein expression in plasma was detected via ELISA. A total of 72 OSCC specimens were recruited in this study for evaluation of correlations of CLIC1 with clinicopathological features and survival.ResultsCLIC1 was significantly overexpressed in tissue and plasma of OSCC patients. It was found that upregulated CLIC1 was distinctly correlated with histological grade, TNM stage, and tumor size. Meanwhile, Kaplan–Meier survival analysis showed that OSCC patients with high CLIC1 expression had remarkably poorer overall survival rate than those with low CLIC1 expression. Multivariate Cox regression analysis revealed that CLIC1 was the independent prognostic factor for overall survival rate of OSCC patients. In addition, Pearson correlation analysis showed that CLIC1 was associated with multiple tumor-associated genes.ConclusionThese results indicated that CLIC1 acts as a molecular target in OSCC and may present a novel diagnostic marker and therapeutic target for OSCC.

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Section: Discussionmentioning

confidence: 99%

Expression of CLIC1 as a potential biomarker for oral squamous cell carcinoma: a preliminary study

Xu¹,

Feng²,

Li³

et al. 2018

OTT

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“…Sections were subjected to immunohistochemical staining using standard techniques as previously described (35). Staining conditions were optimized for each antibody, included a no primary antibody control for each protein and are detailed in supplemental Table S2.…”

Section: Methodsmentioning

confidence: 99%

Quantitative Shotgun Proteomics Unveils Candidate Novel Esophageal Adenocarcinoma (EAC)-specific Proteins

O’Neill

Pak

Pairo-Castineira

et al. 2017

Molecular & Cellular Proteomics

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Esophageal cancer is the eighth most common cancer worldwide and the majority of patients have systemic disease at presentation. Esophageal adenocarcinoma (OAC), the predominant subtype in western countries, is largely resistant to current chemotherapy regimens. Selective markers are needed to enhance clinical staging and to allow targeted therapies yet there are minimal proteomic data on this cancer type. After histological review, lysates from OAC and matched normal esophageal and gastric samples from seven patients were subjected to LC MS/MS after tandem mass tag labeling and OFFGEL fractionation. Patient matched samples of OAC, normal esophagus, normal stomach, lymph node metastases and uninvolved lymph nodes were used from an additional 115 patients for verification of expression by immunohistochemistry (IHC).Over six thousand proteins were identified and quantified across samples. Quantitative reproducibility was excellent between technical replicates and a moderate correlation was seen across samples with the same histology. The quantitative accuracy was verified across the dynamic range for seven proteins by immunohistochemistry (IHC) on the originating tissues. Multiple novel tumor-specific candidates are proposed and EPCAM was verified by IHC.This shotgun proteomic study of OAC used a comparative quantitative approach to reveal proteins highly expressed in specific tissue types. Novel tumor-specific proteins are proposed and EPCAM was demonstrated to be specifically overexpressed in primary tumors and lymph node metastases compared with surrounding normal tissues. This candidate and others proposed in this study could be developed as tumor-specific targets for novel clinical staging and therapeutic approaches.

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“…Dysfunction of tumor suppressors or oncogenes participates in the development and malignant progression of OS (1,3). Therefore, exploration of the underlying mechanisms is urgently required for identifying potential therapeutic targets for OS.…”

Section: Introductionmentioning

confidence: 99%

Suppressive effect of microRNA-138 on the proliferation and invasion of osteosarcoma cells via targeting SIRT1

Yuan

et al. 2017

Experimental and Therapeutic Medicine

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MicroRNAs (miRs), a class of small non-coding RNAs, function as key regulators in gene expression through binding to the 3′-untranslated region (UTR) of their target mRNA, which further leads to translational repression or mRNA degradation. Recently, miR-138 has been found to have a tumor suppressive role in a variety of human malignancies. However, the exact role of miR-138 in regulating the malignant phenotypes of osteosarcoma (OS) has remained to be elucidated. In the present study, reverse-transcription PCR analysis showed that the expression of miR-138 was markedly reduced in OS tissues compared to that in matched adjacent non-tumorous tissues. Furthermore, it was also downregulated in several common OS cell lines, when compared with that in a normal human osteoblast cell line. Overexpression of miR-138 suppressed cell proliferation and invasion and led to a significant decrease in the protein expression of sirtuin 1 (SIRT1), which was further identified as a direct target gene of miR-138 in MG63 cells. Moreover, restoration of SIRT1 expression reversed the suppressive effects of miR-138 on MG63 cell proliferation and invasion. Finally, the expression of SIRT1 was found to be significantly upregulated in OS tissues compared to that in matched adjacent tissues, and SIRT1 levels were inversely correlated with the miR-138 levels in OS tissues. Therefore, the present study demonstrated that miR-138 has a role in inhibiting OS cell proliferation and invasion via directly targeting SIRT1, and suggested that the miR-138/SIRT1 axis may become a promising therapeutic target for OS.

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Quantitative Proteomic Profiling of Pleomorphic Human Sarcoma Identifies CLIC1 as a Dominant Pro-Oncogenic Receptor Expressed in Diverse Sarcoma Types

Cited by 12 publications

References 63 publications

Expression of CLIC1 as a potential biomarker for oral squamous cell carcinoma: a preliminary study

Expression of CLIC1 as a potential biomarker for oral squamous cell carcinoma: a preliminary study

Quantitative Shotgun Proteomics Unveils Candidate Novel Esophageal Adenocarcinoma (EAC)-specific Proteins

Suppressive effect of microRNA-138 on the proliferation and invasion of osteosarcoma cells via targeting SIRT1

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