High Expression of CD109 Antigen Regulates the Phenotype of Cancer Stem-Like Cells/Cancer-Initiating Cells in the Novel Epithelioid Sarcoma Cell Line ESX and Is Related to Poor Prognosis of Soft Tissue Sarcoma

Emori, Makoto; Tsukahara, Tomohide; Murase, Masaki; Kano, Masanobu; Murata, Kenji; Takahashi, Akiko; Kubo, Terufumi; Asanuma, Hiroko; Yasuda, Kazuyo; Kochin, Vitaly; Kaya, Mitsunori; Nagoya, Satoshi; Nishio, Jun; Iwasaki, Hiroshi; Sonoda, Tomoko; Hasegawa, Tadashi; Torigoe, Toshihiko; Wada, Takuro; Yamashita, Toshihiko; Sato, Noriyuki

doi:10.1371/journal.pone.0084187

Cited by 57 publications

(54 citation statements)

References 45 publications

(41 reference statements)

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“…CD109 overexpression promotes accelerated cell growth in oral SCC cells. In addition, oral dysplastic epithelia expressing high levels of CD109 progressed to SCC within 3 years at a high frequency, and a strong correlation was detected between CD109 expression and prognosis in soft tissue sarcomas [10,12]. These findings suggest that CD109 might be involved in the development of several human tumors.…”

Section: Introductionmentioning

confidence: 82%

CD109 attenuates TGF-β1 signaling and enhances EGF signaling in SK-MG-1 human glioblastoma cells

Zhang

Murakumo

Hagiwara

et al. 2015

Biochemical and Biophysical Research Communications

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CD109 is a glycosylphosphatidylinositol-anchored cell surface protein that is frequently detected in squamous cell carcinomas. CD109 is a negative regulator of TGF-β1 signaling in human keratinocytes, and the N-terminal fragment of CD109 secreted from cells after cleavage by the furin protease is important for modulating TGF-β1 signaling. Previously, we found that CD109 is expressed in human glioblastoma cells; however, the role of CD109 in glioblastoma cells is not established. Here, we describe the effects of CD109 in human glioblastoma cell lines. Three glioblastoma cell lines, SK-MG-1, U251MG and MG178, were tested and CD109 overexpression attenuated TGF-β1 signaling and enhanced EGF signaling in SK-MG-1, but not in U251MG or MG178. The N-terminal CD109 fragment in SK-MG-1 was hyperglycosylated compared with that in MG178 or U251MG. The conditioned medium of CD109-overexpressing SK-MG-1, containing the secreted N-terminal CD109, had a negative effect on TGF-β1 signaling in wild-type SK-MG-1 and MG178, whereas it did not show any effect on EGF signaling. In addition, cell surface CD109 interacts with EGF receptor in SK-MG-1 overexpressing CD109, and exhibited enhanced cell migration and invasion. These findings suggest that CD109 attenuates TGF-β1 signaling and enhances EGF signaling in SK-MG-1 cells and that the membrane-anchored CD109 may play major roles in the EGF signaling pathway.

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Section: Introductionmentioning

confidence: 82%

CD109 attenuates TGF-β1 signaling and enhances EGF signaling in SK-MG-1 human glioblastoma cells

Zhang

Murakumo

Hagiwara

et al. 2015

Biochemical and Biophysical Research Communications

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“…Therefore, CD109+ CECs are a potential predictive marker. In another study, Emori et al evaluated the expression of CD109 protein in 80 clinical specimens of soft tissue sarcoma and found a strong correlation between CD109 protein expression and the prognosis [7].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, some studies have suggested that high expression of CD109 antigen regulates the phenotype of cancer stem-like cells/cancer-initiating cells (CSCs/CICs) in the novel epithelioid sarcoma cell line ESX and might be a CSCs/CIC marker in epithelioid sarcoma [7]. The studies indicated that CD109 may be a promising prognostic biomarker and a molecular target of cancer therapy for sarcomas [7].…”

Section: Introductionmentioning

confidence: 99%

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CD109 is a potential target for triple-negative breast cancer

et al. 2014

Tumor Biol.

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The aim of this study is to explore the expression of CD109 in breast cancer stem cells and the relationship between CD109 protein and clinicopathological characteristics of breast cancer. CD44+/CD24- tumor cells (CSCs) were selected by flow cytometry. The protein expression of CD109 was analyzed by immunohistochemistry staining, and the relationship between CD109 and clinicopathological parameters of breast cancer was determined. CD109 positively regulated the proliferation of breast CSCs in vitro, and CD109 protein expression was significantly higher in triple-negative breast cancer (TNBC) compared to non-TNBC (63.78 vs. 3.71 %, P = 0.001). Moreover, CD109 protein expression was related to the histological grade of breast cancer (P = 0.015), whereas age (P = 0.731), tumor size (P = 0.995), clinical stage (P = 0.644), and lymph node metastasis (P = 0.924) were not. In the logistic regression model, histological grade (P = 0.001) and molecular type (P = 0.001) were significantly related to CD109 expression. The patients with high expression of CD109 protein had significantly poorer postoperative disease-specific survival than those with no or low expression of CD109 protein (P = 0.001). In the Cox regression, CD109 was an independent prognostic factor (P = 0.001). CD109 is highly expressed in TNBC and is a potential biomarker for the initiation, progression, and differentiation of breast cancer tumors.

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“…For instance, CD109 (the top positively-correlated gene) has recently identified by proteomic analyses as a metastasis-associated protein marker (35) and was highly expressed in ALDH1 -characterized epithelioid sarcoma CSCs (36). Meanwhile, CDX1 and CDX2 (the two most negatively correlated genes) were reported as putative tumor suppressor genes whose expression was epigenetically repressed in CRC, and reduced expression of CDX1 inhibited CSC stem cell differentiation and thus promoted CSC renewal (35).…”

Section: Discussionmentioning

confidence: 99%

A Composite Gene Expression Signature Optimizes Prediction of Colorectal Cancer Metastasis and Outcome

Schell

Yang²,

Missiaglia

et al. 2016

Clinical Cancer Research

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Purpose We previously found that an epithelial-to-mesenchymal transition (EMT)-based gene expression signature was highly correlated to the first principal component (PC1) of 326 colorectal cancer (CRC) tumors and was prognostic. This study was designed to improve these signatures for better prediction of metastasis and outcome. Experimental Design 468 CRC tumors including all stages (I–IV) and metastatic lesions were used to develop a new prognostic score (ΔPC1.EMT) by subtracting the EMT signature score from its correlated PC1 signature score. The score was validated on six other independent datasets with total 3697 tumors. Results ΔPC1.EMT was found to be far more predictive of metastasis and outcome than its parent scores. It performed well in Stages I–III, amongst MSI subtypes, and across multiple mutation-based subclasses, demonstrating a refined capacity to predict distant metastatic potential in tumors even with a “good” prognosis. For example, in the PETACC-3 clinical trial dataset it predicted worse overall survival in an adjusted multivariable model for Stage III patients (HR by IQR=1.50, 95%CI=1.25–1.81, P=0.000016, N=644). The improved performance of ΔPC1.EMT was related to its propensity of identifying epithelial-like subpopulations as well as mesenchymal-like subpopulations. Biologically, the signature was correlated positively with RAS signaling but negatively with mitochondrial metabolism. ΔPC1.EMT was a “best of assessed” prognostic score when compared to ten other known prognostic signatures. Conclusion The study developed a prognostic signature score with a propensity of detecting non-EMT features, including epithelial cancer stem cell-related properties, thereby improving its potential to predict metastasis and poorer outcome in Stages I-III patients.

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High Expression of CD109 Antigen Regulates the Phenotype of Cancer Stem-Like Cells/Cancer-Initiating Cells in the Novel Epithelioid Sarcoma Cell Line ESX and Is Related to Poor Prognosis of Soft Tissue Sarcoma

Cited by 57 publications

References 45 publications

CD109 attenuates TGF-β1 signaling and enhances EGF signaling in SK-MG-1 human glioblastoma cells

CD109 attenuates TGF-β1 signaling and enhances EGF signaling in SK-MG-1 human glioblastoma cells

CD109 is a potential target for triple-negative breast cancer

A Composite Gene Expression Signature Optimizes Prediction of Colorectal Cancer Metastasis and Outcome

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