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01-12-2015 | Research Article

High expression of valosin-containing protein predicts poor prognosis in patients with breast carcinoma

Authors: Yan Cui, Ming Niu, Xianyu Zhang, Zhenbin Zhong, Ji Wang, Da Pang

Published in: Tumor Biology | Issue 12/2015

Abstract

Valosin-containing protein (VCP) is one of the AAA-ATPase superfamily members. The correlation between elevated expression of VCP and progression, prognosis, and the metastatic potential has been identified in various tumor types. However, the clinical impact of VCP in breast carcinoma has not been investigated. In the current study, the expression of VCP in 421 breast tumors and adjacent normal breast tissues was examined to investigate the correlation between VCP expression and clinicopathological features in patients with breast carcinoma. We found that the expression of VCP correlated with the TNM stage, Ki67 labeling, and lymph node metastasis (LNM). The expression of VCP was increased significantly in the cytoplasm of cancer cells compared to normal mammary epithelial cells, which was associated with decreased overall survival rates of patients with breast carcinoma (P < 0.001). In conclusion, this study demonstrates significant correlation between the cytoplasmic expression of VCP and adverse prognosis in breast carcinoma, suggesting that VCP may serve as a prognostic biomarker in breast carcinoma.

Cancer IAfRo. Latest world cancer statistics global cancer burden rises to 14.1 million new cases in 2012: marked increase in breast cancers must be addressed. World Health Organization 2013:1–3.

Xu Y, Hu B, Qin L, Zhao L, Wang Q, Wang Q, et al. Src-1 and twist1 expression positively correlates with a poor prognosis in human breast cancer. Int J Biol Sci. 2014;10:396–403.CrossRefPubMedPubMedCentral

Meyer H, Bug M, Bremer S. Emerging functions of the VCP/p97 AAA-ATPase in the ubiquitin system. Nat Cell Biol. 2012;14:117–23.CrossRefPubMed

Min T, Bodas M, Mazur S, Vij N. Critical role of proteostasis-imbalance in pathogenesis of COPD and severe emphysema. J Mol Med (Berl). 2011;89:577–93.CrossRef

Ishigaki S, Hishikawa N, Niwa J-I, Iemura S-I, Natsume T, Hori S, et al. Physical and functional interaction between dorfin and valosin-containing protein that are colocalized in ubiquitylated inclusions in neurodegenerative disorders. J Biol Chem. 2004;279:51376–85.CrossRefPubMed

Vij N. AAA ATPase p97/VCP: cellular functions, disease and therapeutic potential. J Cell Mol Med. 2008;12:2511–8.CrossRefPubMedPubMedCentral

Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 2008;321:1801–6.CrossRefPubMedPubMedCentral

Yamamoto S, Tomita Y, Hoshida Y, Iizuka N, Kidogami S, Miyata H, et al. Expression level of valosin-containing protein (p97) is associated with prognosis of esophageal carcinoma. Clin Cancer Res. 2004;10:5558–65.CrossRefPubMed

Yamamoto S, Tomita Y, Hoshida Y, Sakon M, Kameyama M, Imaoka S, et al. Expression of valosin-containing protein in colorectal carcinomas as a predictor for disease recurrence and prognosis. Clin Cancer Res. 2004;10:651–7.CrossRefPubMed

10.

Yi P, Higa A, Taouji S, Bexiga MG, Marza E, Arma D, et al. Sorafenib-mediated targeting of the AAA(+) ATPase p97/VCP leads to disruption of the secretory pathway, endoplasmic reticulum stress, and hepatocellular cancer cell death. Mol Cancer Ther. 2012;11:2610–20.CrossRefPubMed

11.

Tsujimoto Y, Tomita Y, Hoshida Y, Kono T, Oka T, Yamamoto S, et al. Elevated expression of valosin-containing protein (p97) is associated with poor prognosis of prostate cancer. Clin Cancer Res. 2004;10:3007–12.CrossRefPubMed

12.

Dai RM, Chen E, Longo DL, Gorbea CM, Li CC. Involvement of valosin-containing protein, an atpase co-purified with ikappaBalpha and 26 s proteasome, in ubiquitin-proteasome-mediated degradation of ikappaBalpha. J Biol Chem. 1998;273:3562–73.CrossRefPubMed

13.

Dai RM, Li C-CH. Valosin-containing protein is a multi-ubiquitin chain-targeting factor required in ubiquitin–proteasome degradation. Nat Cell Biol. 2001;3:740–4.CrossRefPubMed

14.

Karin M, Yamamoto Y, Wang QM. The IKK NF-κB system: a treasure trove for drug development. Nat Rev Drug Discov. 2004;3:17–26.CrossRefPubMed

15.

Beg AA, Baltimore D. An essential role for NF-kappaB in preventing TNF-alpha-induced cell death. Science. 1996;274:782–4.CrossRefPubMed

16.

Luo J, Manning BD, Cantley LC. Targeting the PI3K-Akt pathway in human cancer-rationale and promise. Cancer Cell. 2003;4:257–62.CrossRefPubMed

17.

Klein JB, Barati MT, Wu R, Gozal D, Sachleben Jr LR, Kausar H, et al. Akt-mediated valosin-containing protein 97 phosphorylation regulates its association with ubiquitinated proteins. J Biol Chem. 2005;280:31870–81.CrossRefPubMed

18.

Matkovic B, Juretic A, Separovic V, Novosel I, Separovic R, Gamulin M, et al. Immunohistochemical analysis of ER, PR, HER-2, CK 5/6, p63 and EGFR antigen expression in medullary breast cancer. Tumori. 2008;94:838–44.PubMed

19.

Hsu C-Y, Ho DM-T, Yang C-F, Lai C-R, Yu I-T, Chiang H. Interobserver reproducibility of Her-2/neu protein overexpression in invasive breast carcinoma using the DAKO HercepTest®. Am J Clin Pathol. 2002;118:693–8.CrossRefPubMed

20.

Cheang MC, Chia SK, Voduc D, Gao D, Leung S, Snider J, et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst. 2009;101:736–50.CrossRefPubMedPubMedCentral

21.

Simon R, Mirlacher M, Sauter G. Tissue microarrays; molecular diagnosis of cancer, Springer, 2004, pp 377–89.

22.

Fessart D, Marza E, Taouji S, Delom F, Chevet E. P97/CDC-48: proteostasis control in tumor cell biology. Cancer Lett. 2013;337:26–34.CrossRefPubMed

23.

Asai T, Tomita Y, Nakatsuka SI, Hoshida Y, Myoui A, Yoshikawa H, et al. VCP (p97) regulates NFkB signaling pathway, which is important for metastasis of osteosarcoma cell line. Cancer Sci. 2002;93:296–304.

24.

Xu S, Peng G, Wang Y, Fang S, Karbowski M. The AAA-ATPase p97 is essential for outer mitochondrial membrane protein turnover. Mol Biol Cell. 2011;22:291–300.CrossRefPubMedPubMedCentral

25.

Rumpf S, Lee SB, Jan LY, Jan YN. Neuronal remodeling and apoptosis require VCP-dependent degradation of the apoptosis inhibitor DIAP1. Development. 2011;138:1153–60.CrossRefPubMedPubMedCentral

26.

Biswas DK, Shi Q, Baily S, Strickland I, Ghosh S, Pardee AB, et al. NF-κB activation in human breast cancer specimens and its role in cell proliferation and apoptosis. Proc Natl Acad Sci U S A. 2004;101:10137–42.CrossRefPubMedPubMedCentral

27.

Shostak K, Chariot A. NF-kappaB, stem cells and breast cancer: the links get stronger. Breast Cancer Res. 2011;13:214.CrossRefPubMedPubMedCentral

28.

Li T, Lu H, Shen C, Lahiri S, Wason M, Mukherjee D, et al. Identification of epithelial stromal interaction 1 as a novel effector downstream of Krüppel-like factor 8 in breast cancer invasion and metastasis. Oncogene 2013.

29.

Vandermoere F, El Yazidi-Belkoura I, Slomianny C, Demont Y, Bidaux G, Adriaenssens E, et al. The valosin-containing protein (VCP) is a target of Akt signaling required for cell survival. J Biol Chem. 2006;281:14307–13.CrossRefPubMed

30.

Bose S, Chandran S, Mirocha JM, Bose N. The Akt pathway in human breast cancer: a tissue-array-based analysis. Mod Pathol. 2006;19:238–45.CrossRefPubMed

31.

Meyer MF, Seuthe IM, Drebber U, Siefer O, Kreppel M, Klein MO, et al. Valosin-containing protein (VCP/p97)-expression correlates with prognosis of HPV-negative oropharyngeal squamous cell carcinoma (OSCC). PLoS One. 2014;9, e114170.CrossRefPubMedPubMedCentral

32.

Zhu WW, Kang L, Gao YP, Hei Y, Dong J, Liu Y, et al. Expression level of valosin containing protein is associated with prognosis of primary orbital MALT lymphoma. Asian Pac J Cancer Prev. 2013;14:6439–43.CrossRefPubMed

33.

Liu Y, Hei Y, Shu Q, Dong J, Gao Y, Fu H, et al. VCP/p97, down-regulated by microRNA-129-5p, could regulate the progression of hepatocellular carcinoma. PLoS One. 2012;7, e35800.CrossRefPubMedPubMedCentral

34.

Valle CW, Min T, Bodas M, Mazur S, Begum S, Tang D, et al. Critical role of VCP/p97 in the pathogenesis and progression of non-small cell lung carcinoma. PLoS One. 2011;6, e29073.CrossRefPubMedPubMedCentral

Title: High expression of valosin-containing protein predicts poor prognosis in patients with breast carcinoma
Authors: Yan Cui
Ming Niu
Xianyu Zhang
Zhenbin Zhong
Ji Wang
Da Pang
Publication date: 01-12-2015
Publisher: Springer Netherlands
Published in: Tumor Biology / Issue 12/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-015-3748-9

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