Skip to main content
Erschienen in: Digestive Diseases and Sciences 8/2016

13.04.2016 | Original Article

RETRACTED ARTICLE: CD109 Mediates Cell Survival in Hepatocellular Carcinoma Cells

verfasst von: Guijuan Zong, Zhiwei Xu, Shusen Zhang, Yifen Shen, Huiyuan Qiu, Guizhou Zhu, Song He, Tao Tao, Xudong Chen

Erschienen in: Digestive Diseases and Sciences | Ausgabe 8/2016

Einloggen, um Zugang zu erhalten

Abstract

Background

Hepatocellular carcinoma (HCC) accounts for 75–80 % of primary liver cancer, and usually arises after years of liver disease. Thus it is important to understand the molecular mechanisms which drive or mediate the development of HCC.

Aim

In this work, we examined whether CD109 was associated with a poor prognosis in HCC and explored possible underlying mechanisms.

Methods

We examined the CD109 and Ki67 expression levels in 97 patients with HCC using immunohistochemistry. CD109 levels in HCC cells were down-regulated by shRNA transfection. The cycle progression and cell proliferation status of HCC cells were evaluated by flow cytometry and CCK-8 assay. The effect of CD109 on proliferation and apoptosis was investigated by western blot and TUNEL activity assays.

Results

The CD109 protein was up-regulated in HCC tissue compared with adjacent noncancerous tissue. CD109 expression levels in the 97 patients with HCC were positively correlated with histological grade. Univariate and multivariate survival analysis revealed that CD109 was a significant predictor of overall survival among HCC patients. CD109 shRNA knockdown delayed the G1–S phase transition, abrogated cell proliferation, and increased cell apoptosis. Furthermore, CD109 impaired TGF-β/Smad signaling through control of p-smad2.

Conclusions

CD109 promoted HCC proliferation and predicted poor prognosis. In addition, CD109 expression was associated with anti-apoptosis in HCC cells.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Tsao CM, et al. SOX1 functions as a tumor suppressor by antagonizing the WNT/beta-catenin signaling pathway in hepatocellular carcinoma. Hepatology. 2012;56:2277–2287.CrossRef Tsao CM, et al. SOX1 functions as a tumor suppressor by antagonizing the WNT/beta-catenin signaling pathway in hepatocellular carcinoma. Hepatology. 2012;56:2277–2287.CrossRef
2.
Zurück zum Zitat Cheng AS, et al. EZH2-mediated concordant repression of Wnt antagonists promotes beta-catenin-dependent hepatocarcinogenesis. Cancer Res. 2011;71:4028–4039.CrossRef Cheng AS, et al. EZH2-mediated concordant repression of Wnt antagonists promotes beta-catenin-dependent hepatocarcinogenesis. Cancer Res. 2011;71:4028–4039.CrossRef
3.
Zurück zum Zitat Zhang J, et al. Cancer specific long noncoding RNAs show differential expression patterns and competing endogenous RNA potential in hepatocellular carcinoma. PLoS One. 2015;10:e0141042.CrossRef Zhang J, et al. Cancer specific long noncoding RNAs show differential expression patterns and competing endogenous RNA potential in hepatocellular carcinoma. PLoS One. 2015;10:e0141042.CrossRef
4.
Zurück zum Zitat Hagikura M, et al. Correlation of pathological grade and tumor stage of urothelial carcinomas with CD109 expression. Pathol Int. 2010;60:735–743.CrossRef Hagikura M, et al. Correlation of pathological grade and tumor stage of urothelial carcinomas with CD109 expression. Pathol Int. 2010;60:735–743.CrossRef
5.
Zurück zum Zitat Lin M, et al. Cell surface antigen CD109 is a novel member of the alpha(2) macroglobulin/C3, C4, C5 family of thioester-containing proteins. Blood. 2002;99:1683–1691.CrossRef Lin M, et al. Cell surface antigen CD109 is a novel member of the alpha(2) macroglobulin/C3, C4, C5 family of thioester-containing proteins. Blood. 2002;99:1683–1691.CrossRef
6.
Zurück zum Zitat Hashimoto M, et al. Expression of CD109 in human cancer. Oncogene. 2004;23:3716–3720.CrossRef Hashimoto M, et al. Expression of CD109 in human cancer. Oncogene. 2004;23:3716–3720.CrossRef
7.
Zurück zum Zitat Beije N, et al. Prognostic value and kinetics of circulating endothelial cells in patients with recurrent glioblastoma randomised to bevacizumab plus lomustine, bevacizumab single agent or lomustine single agent. A report from the Dutch Neuro-Oncology Group BELOB trial. Br J Cancer. 2015;113:226–231.CrossRef Beije N, et al. Prognostic value and kinetics of circulating endothelial cells in patients with recurrent glioblastoma randomised to bevacizumab plus lomustine, bevacizumab single agent or lomustine single agent. A report from the Dutch Neuro-Oncology Group BELOB trial. Br J Cancer. 2015;113:226–231.CrossRef
8.
Zurück zum Zitat Hwang SM, et al. Human platelet antigen genotyping and expression of CD109 (human platelet antigen 15) mRNA in various human cell types. Biomed Res Int. 2013;2013:946403.CrossRef Hwang SM, et al. Human platelet antigen genotyping and expression of CD109 (human platelet antigen 15) mRNA in various human cell types. Biomed Res Int. 2013;2013:946403.CrossRef
9.
Zurück zum Zitat Hagiwara S, et al. Processing of CD109 by furin and its role in the regulation of TGF-beta signaling. Oncogene. 2010;29:2181–2191.CrossRef Hagiwara S, et al. Processing of CD109 by furin and its role in the regulation of TGF-beta signaling. Oncogene. 2010;29:2181–2191.CrossRef
10.
Zurück zum Zitat Chan KS, et al. Identification, molecular characterization, clinical prognosis, and therapeutic targeting of human bladder tumor-initiating cells. Proc Natl Acad Sci USA. 2009;106:14016–14021.CrossRef Chan KS, et al. Identification, molecular characterization, clinical prognosis, and therapeutic targeting of human bladder tumor-initiating cells. Proc Natl Acad Sci USA. 2009;106:14016–14021.CrossRef
11.
Zurück zum Zitat Ohshima Y, et al. CD109 expression levels in malignant melanoma. J Dermatol Sci. 2010;57:140–142.CrossRef Ohshima Y, et al. CD109 expression levels in malignant melanoma. J Dermatol Sci. 2010;57:140–142.CrossRef
12.
Zurück zum Zitat Cuppini L, et al. Prognostic value of CD109+ circulating endothelial cells in recurrent glioblastomas treated with bevacizumab and irinotecan. PLoS One. 2013;8:e74345.CrossRef Cuppini L, et al. Prognostic value of CD109+ circulating endothelial cells in recurrent glioblastomas treated with bevacizumab and irinotecan. PLoS One. 2013;8:e74345.CrossRef
13.
Zurück zum Zitat Xu Z, et al. USP11, deubiquitinating enzyme, associated with neuronal apoptosis following intracerebral hemorrhage. J Mol Neurosci. 2016;58:16–27.CrossRef Xu Z, et al. USP11, deubiquitinating enzyme, associated with neuronal apoptosis following intracerebral hemorrhage. J Mol Neurosci. 2016;58:16–27.CrossRef
14.
Zurück zum Zitat Xu Z, et al. Upregulated expression of karyopherin alpha2 is involved in neuronal apoptosis following intracerebral hemorrhage in adult rats. Cell Mol Neurobiol. 2015. [Epub ahead of print]. doi:10.1007/s10571-015-0258-7. Xu Z, et al. Upregulated expression of karyopherin alpha2 is involved in neuronal apoptosis following intracerebral hemorrhage in adult rats. Cell Mol Neurobiol. 2015. [Epub ahead of print]. doi:10.​1007/​s10571-015-0258-7.
15.
Zurück zum Zitat Zhang S, et al. Overexpression of SYF2 correlates with enhanced cell growth and poor prognosis in human hepatocellular carcinoma. Mol Cell Biochem. 2015;410:1–9. Zhang S, et al. Overexpression of SYF2 correlates with enhanced cell growth and poor prognosis in human hepatocellular carcinoma. Mol Cell Biochem. 2015;410:1–9.
16.
Zurück zum Zitat Sciarra A, et al. Morphophenotypic changes in human multistep hepatocarcinogenesis with translational implications. J Hepatol. 2016;64:87–93.CrossRef Sciarra A, et al. Morphophenotypic changes in human multistep hepatocarcinogenesis with translational implications. J Hepatol. 2016;64:87–93.CrossRef
17.
Zurück zum Zitat Tan HY, et al. Autophagy-induced RelB/p52 activation mediates tumour-associated macrophage repolarisation and suppression of hepatocellular carcinoma by natural compound baicalin. Cell Death Dis. 2015;6:e1942.CrossRef Tan HY, et al. Autophagy-induced RelB/p52 activation mediates tumour-associated macrophage repolarisation and suppression of hepatocellular carcinoma by natural compound baicalin. Cell Death Dis. 2015;6:e1942.CrossRef
18.
Zurück zum Zitat Zhang F, et al. SWATH- and iTRAQ-based quantitative proteomic analyses reveal an overexpression and biological relevance of CD109 in advanced NSCLC. J Proteomics. 2014;102:125–136.CrossRef Zhang F, et al. SWATH- and iTRAQ-based quantitative proteomic analyses reveal an overexpression and biological relevance of CD109 in advanced NSCLC. J Proteomics. 2014;102:125–136.CrossRef
19.
Zurück zum Zitat Dong F, et al. CD109 expression is increased in cutaneous squamous cell carcinoma. J Dermatol. 2014;41:947–949.CrossRef Dong F, et al. CD109 expression is increased in cutaneous squamous cell carcinoma. J Dermatol. 2014;41:947–949.CrossRef
20.
Zurück zum Zitat Zhang JM, et al. CD109 attenuates TGF-beta1 signaling and enhances EGF signaling in SK-MG-1 human glioblastoma cells. Biochem Biophys Res Commun. 2015;459:252–258.CrossRef Zhang JM, et al. CD109 attenuates TGF-beta1 signaling and enhances EGF signaling in SK-MG-1 human glioblastoma cells. Biochem Biophys Res Commun. 2015;459:252–258.CrossRef
21.
Zurück zum Zitat Winocour S, et al. CD109, a novel TGF-beta antagonist, decreases fibrotic responses in a hypoxic wound model. Exp Dermatol. 2014;23:475–479.CrossRef Winocour S, et al. CD109, a novel TGF-beta antagonist, decreases fibrotic responses in a hypoxic wound model. Exp Dermatol. 2014;23:475–479.CrossRef
22.
Zurück zum Zitat Bizet AA, et al. CD109-mediated degradation of TGF-beta receptors and inhibition of TGF-beta responses involve regulation of SMAD7 and Smurf2 localization and function. J Cell Biochem. 2012;113:238–246.CrossRef Bizet AA, et al. CD109-mediated degradation of TGF-beta receptors and inhibition of TGF-beta responses involve regulation of SMAD7 and Smurf2 localization and function. J Cell Biochem. 2012;113:238–246.CrossRef
23.
Zurück zum Zitat Bizet AA, et al. The TGF-beta co-receptor, CD109, promotes internalization and degradation of TGF-beta receptors. Biochim Biophys Acta. 2011;1813:742–753.CrossRef Bizet AA, et al. The TGF-beta co-receptor, CD109, promotes internalization and degradation of TGF-beta receptors. Biochim Biophys Acta. 2011;1813:742–753.CrossRef
24.
Zurück zum Zitat Yan HH, et al. CCL9 induced by TGF-beta signaling in myeloid cells enhances tumor cell survival in the premetastatic organ. Cancer Res. 2015;75:5283–5298.CrossRef Yan HH, et al. CCL9 induced by TGF-beta signaling in myeloid cells enhances tumor cell survival in the premetastatic organ. Cancer Res. 2015;75:5283–5298.CrossRef
25.
Zurück zum Zitat Wang XH, et al. TGF-beta1 pathway affects the protein expression of many signaling pathways, markers of liver cancer stem cells, cytokeratins, and TERT in liver cancer HepG cells. Tumour Biol. 2015. [Epub ahead of print]. Wang XH, et al. TGF-beta1 pathway affects the protein expression of many signaling pathways, markers of liver cancer stem cells, cytokeratins, and TERT in liver cancer HepG cells. Tumour Biol. 2015. [Epub ahead of print].
26.
Zurück zum Zitat Riemenschneider MJ, et al. TGF-ss isoforms in cancer: immunohistochemical expression and Smad-pathway-activity-analysis in thirteen major tumor types with a critical appraisal of antibody specificity and immunohistochemistry assay validity. Oncotarget. 2015;6:26770–26781.CrossRef Riemenschneider MJ, et al. TGF-ss isoforms in cancer: immunohistochemical expression and Smad-pathway-activity-analysis in thirteen major tumor types with a critical appraisal of antibody specificity and immunohistochemistry assay validity. Oncotarget. 2015;6:26770–26781.CrossRef
27.
Zurück zum Zitat Dong F, et al. CD109 is a novel marker for squamous cell/adenosquamous carcinomas of the gallbladder. Diagn Pathol. 2015;10:137.CrossRef Dong F, et al. CD109 is a novel marker for squamous cell/adenosquamous carcinomas of the gallbladder. Diagn Pathol. 2015;10:137.CrossRef
28.
Zurück zum Zitat Litvinov IV, et al. CD109 release from the cell surface in human keratinocytes regulates TGF-beta receptor expression, TGF-beta signalling and STAT3 activation: relevance to psoriasis. Exp Dermatol. 2011;20:627–632.CrossRef Litvinov IV, et al. CD109 release from the cell surface in human keratinocytes regulates TGF-beta receptor expression, TGF-beta signalling and STAT3 activation: relevance to psoriasis. Exp Dermatol. 2011;20:627–632.CrossRef
29.
Zurück zum Zitat van den Hoogen C, et al. High aldehyde dehydrogenase activity identifies tumor-initiating and metastasis-initiating cells in human prostate cancer. Cancer Res. 2010;70:5163–5173.CrossRef van den Hoogen C, et al. High aldehyde dehydrogenase activity identifies tumor-initiating and metastasis-initiating cells in human prostate cancer. Cancer Res. 2010;70:5163–5173.CrossRef
Metadaten
Titel
RETRACTED ARTICLE: CD109 Mediates Cell Survival in Hepatocellular Carcinoma Cells
verfasst von
Guijuan Zong
Zhiwei Xu
Shusen Zhang
Yifen Shen
Huiyuan Qiu
Guizhou Zhu
Song He
Tao Tao
Xudong Chen
Publikationsdatum
13.04.2016
Erschienen in
Digestive Diseases and Sciences / Ausgabe 8/2016
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-016-4149-7

Weitere Artikel der Ausgabe 8/2016

Digestive Diseases and Sciences 8/2016 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.