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http://dx.doi.org/10.7314/APJCP.2014.15.2.989

Aberrant Expression of the Autocrine Motility Factor Receptor Correlates with Poor Prognosis and Promotes Metastasis in Gastric Carcinoma  

Huang, Zhen (Department of Gastrointestinal Surgery, the First Affiliated Hospital of Chongqing Medical University)
Zhang, Neng (Department of Gastrointestinal Surgery, the First Affiliated Hospital of Chongqing Medical University)
Zha, Lang (Department of Gastrointestinal Surgery, the First Affiliated Hospital of Chongqing Medical University)
Mao, Hong-Chao (Department of Gastrointestinal Surgery, the First Affiliated Hospital of Chongqing Medical University)
Chen, Xuan (Department of Gastrointestinal Surgery, the First Affiliated Hospital of Chongqing Medical University)
Xiang, Ji-Feng (Department of Gastrointestinal Surgery, the First Affiliated Hospital of Chongqing Medical University)
Zhang, Hua (Department of Gastrointestinal Surgery, the First Affiliated Hospital of Chongqing Medical University)
Wang, Zi-Wei (Department of Gastrointestinal Surgery, the First Affiliated Hospital of Chongqing Medical University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.2, 2014 , pp. 989-997 More about this Journal
Abstract
AMFR, autocrine motility factor receptor, also called gp78, is a cell surface cytokine receptor which has a dual role as an E3 ubiquitin ligase in endoplasmic reticulum-associated degradation. AMFR expression is associated with tumor malignancy. We here investigated the clinical significance of AMFR and its role in metastasis and prognosis in gastric cancer. Expression of AMFR, E-cadherin and N-cadherin in cancer tissues and matched adjacent normal tissues from 122 gastric cancer (GC) patients undergoing surgical resection was assessed by immunohistochemistry. Levels of these molecules in 17 cases selected randomly were also analysed by Western blotting. AMFR expression was significantly increased in gastric cancer tissues, and associated with invasion depth and lymph node metastasis. Kaplan-Meier analysis showed AMFR expression correlated with poor overall survival and an increased risk of recurrence in the GC cases. Cox regression analysis suggested AMFR to be an independent predictor for overall and recurrence-free survival. E-cadherin expression was decreased in gastric cancer tissues; conversely, N-cadherin was increased. Expression of AMFR negatively correlated with E-cadherin expression, whereas N-cadherin expression showed a significant positive correlation with AMFR expression. AMFR might be involved in the regulation of epithelial-mesenchymal transition, with aberrant expression correlating with a poor prognosis and promoting invasion and metastasis in GCs.
Keywords
Gastric carcinoma; AMFR; prognosis; metastasis; epithelial-mesenchymal transition;
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1 Chen B, Mariano J, Tsai YC, et al (2006). The activity of a human endoplasmic reticulum-associated degradation E3, gp78, requires its Cue domain, RING finger, and an E2-binding site. Proc Natl Acad Sci USA, 103, 341-6.   DOI   ScienceOn
2 Chiu CG, St-Pierre P, Nabi IR, Wiseman SM (2008). Autocrine motility factor receptor: a clinical review. Expert Rev Anticancer Ther, 8, 207-17.   DOI   ScienceOn
3 Das R, Mariano J, Tsai YC, et al (2009). Allosteric activation of E2-RING finger-mediated ubiquitylation by a structurally defined specific E2-binding region of gp78. Mol Cell, 34, 674-85.   DOI   ScienceOn
4 Fang S, Ferrone M, Yang C, et al (2001). The tumor autocrine motility factor receptor, gp78, is a ubiquitin protein ligase implicated in degradation from the endoplasmic reticulumProc. Proc Natl Acad Sci USA, 98, 14422-7.   DOI   ScienceOn
5 Berx G, van Roy F (2009). Involvement of members of the cadherin superfamily in cancer. Cold Spring Harb Perspect Biol, 1, a003129.
6 Cai J, Zhao XL, Liu AW, Nian H, Zhang SH (2011). Apigenin inhibits hepatoma cell growth through alteration of gene expression patterns. Phytomedicine, 18, 366-73.   DOI   ScienceOn
7 Funasaka T, Haga A, Raz A, Nagase H (2001). Tumor autocrine motility factor is an angiogenic factor that stimulates endothelial cell motility. Biochem Biophys Res Commun, 285, 118-28.   DOI   ScienceOn
8 Funasaka T, Haga A, Raz A, Nagase H (2002). Autocrine motility factor secreted by tumor cells upregulates vascular endothelial growth factor receptor (Flt-1) expression in endothelial cells. Int J Cancer, 101, 217-23.   DOI   ScienceOn
9 Niinaka Y, Paku S, Haga A, Watanabe H, Raz A (1998). Expression and secretion of neuroleukin/phosphohexose isomerase/maturation factor as autocrine motility factor by tumor cells. Cancer Res, 58, 2667-74.
10 Morito D, Hirao K, Oda Y, et al (2008). Gp78 cooperates with RMA1 in endoplasmic reticulum-associated degradation of CFTRDeltaF508. Mol Biol Cell, 19, 1328-36.   DOI   ScienceOn
11 Nakatsukasa K, Brodsky JL (2008). The recognition and retrotranslocation of misfolded proteins from the endoplasmic reticulum. Traffic, 9, 861-70.   DOI   ScienceOn
12 Nussenbaum F, Herman IM (2010). Tumor angiogenesis: insights and innovations. J Oncol, 2010, 132641.
13 Peng CW, Wang LW, Zeng WJ, Yang XJ, Li Y (2013). Evaluation of the staging systems for gastric cancer. J Surg Oncol, 108, 93-105.   DOI   ScienceOn
14 Romagnolia A, Oliverio S, Evangelisti C, et al (2003). Neuroleukin inhibition sensitises neuronal cells to caspasedependent apoptosis. Biochem Biophys Res Commun, 302, 448-53.   DOI   ScienceOn
15 Saito H, Fukumoto Y, Osaki T, et al (2008). Prognostic significance of the ratio between metastatic and dissected lymph nodes (n ratio) in patients with advanced gastric cancer. J Surg Oncol, 97, 132-5.   DOI   ScienceOn
16 Shimizu K, Tani M, Watanabe H, et al (1999). The autocrine motility factor gene encodes a novel type of seven transmembrane protein. FEBS Lett, 456, 295-300.   DOI   ScienceOn
17 Cavallaro U, Christofori G (2004). Cell adhesion and signalling by cadherins and Ig-CAMs in cancer. Nat Rev Cancer, 4, 118-32.   DOI   ScienceOn
18 Jemal A, Bray F, Center MM, et al (2011). Global Cancer Statistics. CA Cancer J Clin, 61, 69-90.   DOI
19 Zha L, Zhang J, Tang W, et al (2013). HMGA2 elicits EMT by activating the Wnt/$\beta$-catenin pathway in gastric cancer. Dig Dis Sci, 58, 724-33.   DOI   ScienceOn
20 Zhang N, Zhang J, Wang ZW, Zha L, Huang Z (2012). Altered expression of Kruppel-like factor 4 and $\beta$-catenin in human gastric cancer. Oncol Lett, 3, 1017-22.
21 Iiizumi M, Liu W, Pai SK, Furuta E, Watabe K (2008). Drug development against metastasis-related genes and their pathways: a rationale for cancer therapy. Biochim Biophys Acta, 1786, 87-104.
22 Joshi B, Li L, Nabi IR (2010). A role for KAI1 in promotion of cell proliferation and mammary gland hyperplasia by the gp78 ubiquitin ligase. J Biol Chem, 285, 8830-9.   DOI   ScienceOn
23 Kostova Z, Tsai YC, Weissman AM (2007). Ubiquitin ligases, critical mediators of endoplasmic reticulum-associated degradation. Semin Cell Dev Biol, 18, 770-79.   DOI   ScienceOn
24 Li FX, Zhang RP, Liang H, et al (2013). Validity and necessity of sub-classification of N3 in the 7th UICC TNM stage of gastric cancer. Asian Pac J Cancer Prev, 14, 2091-5.   DOI   ScienceOn
25 Liang JS, Kim T, Fang S, et al (2003). Overexpression of the tumor autocrine motility factor receptor Gp78, a ubiquitin protein ligase, results in increased ubiquitinylation and decreased secretion of apolipoprotein B100 in HepG2 cells. J Biol Chem, 278, 23984-8.   DOI   ScienceOn
26 Liotta LA, Mandler R, Murano G, et al (1986). Tumor cell autocrine motility factor. Proc Natl Acad Sci USA, 83, 3302-6.   DOI
27 Miranti CK (2009). Controlling cell surface dynamics and signaling: how CD82/KAI1 suppresses metastasis. Cell Signal, 21, 196-211.   DOI   ScienceOn
28 Watanabe H, Carmi P, Hogan V, et al (1991). Purification of human tumor cell autocrine motility factor and molecular cloning of its receptor. J Biol Chem, 266, 13442-8.
29 Tsutsumi S, Yanagawa T, Shimura T, et al (2003). Regulation of cell proliferation by autocrine motility factor/phosphoglucose isomerase signaling. J Biol Chem, 278, 32165-72.   DOI   ScienceOn
30 Tsutsumi S, Gupta SK, Hogan V, Collard JG, Raz A (2002). Activation of small GTPase Rho is required for autocrine motility factor signaling. Cancer Res, 62, 4484-90.
31 Wallace TA, Prueitt RL, Yi M, et al (2008). Tumor immunobiological differences in prostate cancer between African-American and European-American men. Cancer Res, 68, 927-36.   DOI   ScienceOn
32 Watanabe H, Takehama K, Date M, Shinozaki T, Raz A (1996). Tumor cell motility factor is the neuroleukin/ phosphohexose isomerase polypeptide. Cancer Res, 56, 2960-3.
33 Wei D, Gong W, Kanai M, et al (2005). Drastic down-regulation of kruppel-like factor 4 expression is critical in human gastric cancer development and progression. Cancer Res, 65, 2746-54.   DOI   ScienceOn
34 World Health Organization (2008). The global burden of disease: 2004 update. Geneva: World Health Organization.
35 Yilmaz M, Christofori G (2009). EMT, the cytoskeleton, and cancer cell invasion. Cancer Metastasis Rev, 28, 15-33.   DOI   ScienceOn
36 Zhong X, Shen Y, Ballar P, et al (2004). AAA ATPase p97/ valosin-containing protein interacts with gp78, a ubiquitin ligase for endoplasmic reticulum-associated degradation. J Biol Chem, 279, 45676-84.   DOI   ScienceOn
37 Siegel R, Naishadham MA, Jemal A (2013). Cancer Statistics, 2013. CA Cancer J Clin, 63, 11-30.   DOI   ScienceOn
38 Silletti S, Watanabe H, Hogan V, Nabi IR, Raz A (1991). Purification of B16-F1 melanoma autocrine motility factor and its receptor. Cancer Res, 51, 3507-11.
39 Song BL, Sever N, DeBose-Boyd RA (2005). Gp78, a membrane-anchored ubiquitin ligase, associates with Insig-1 and couples sterol-regulated ubiquitination to degradation of HMG CoA reductase. Mol Cell, 19, 829-40.   DOI   ScienceOn
40 Sjoblom T, Jones S, Wood LD, et al (2006). The consensus coding sequences of human breast and colorectal cancers. Science, 314, 268-74.   DOI   ScienceOn
41 Sud R, Wells D, Talbot IC, Delhanty JD (2001). Genetic alterations in gastric cancers from British patients. Cancer Genet Cytogenet, 126, 111-9.   DOI   ScienceOn
42 Tahara E (2000). Molecular aspects of invasion and metastasis of stomach cancer. Verh Dtsch Ges Pathol, 84, 43-9.
43 Thiery JP, Acloque H, Huang RY, Nieto MA (2009). Epithelialmesenchymal transitions in development and disease. Cell, 139, 871-90.   DOI   ScienceOn
44 Tsai YC, Mendoza A, Mariano JM, et al (2007). The ubiquitin ligase gp78 promotes sarcoma metastasis by targeting KAI1 for degradation. Nat Med, 13, 1504-9.   DOI   ScienceOn
45 Haga A, Funasaka T, Niinaka Y, Raz A, Nagase H (2003). The autocrine motility factor signaling induces tumor apoptotic resistance which regulates apoptosome expression. Int J Cancer, 107, 707-14.   DOI   ScienceOn
46 Haga A, Niinaka Y, Raz A (2000). Phosphohexose isomerase/autocrine motility factor/neuroleukin/ maturation factor is a multifunctional phosphoprotein. Biochim Biophys Acta, 1480, 235-44.   DOI   ScienceOn
47 Funasaka T, Hu H, Yanagawa T, Hogan V, Raz A (2007). Downregulation of phosphoglucose isomerase/autocrine motility factor results in mesenchymal-to-epithelial transition of human lung fibrosarcoma cells. Cancer Res, 67, 4236-43.   DOI   ScienceOn
48 Graziosi L, Marino E, Cavazzoni E, Donini A (2013). Prognostic value of the seventh AJCC/UICC TNM classification of noncardia gastric cancer. World J Surg Oncol, 11, 103.   DOI   ScienceOn
49 Hanahan D, Weinberg RA (2011). Hallmarks of cancer: the next generation. Cell, 144, 646-74.   DOI   ScienceOn
50 Hlubek F, Brabletz T, Budczies J, et al. Heterogeneous expression of Wnt/beta-catenin target genes within colorectal cancer. Int J Cancer, 121, 1941-8.
51 Fairbank M, St-Pierre P, Nabi IR (2009). The complex biology of autocrine motility factor/ phosphoglucose isomerase (AMF/PGI) and its receptor, the gp78/AMFR E3 ubiquitin ligase. Mol Biosyst, 5, 793-801.   DOI   ScienceOn
52 Murray D, Horgan G, Macmathuna P, Doran P (2008). NET1-mediated RhoA activation facilitates lysophosphatidic acidinduced cell migration and invasion in gastric cancer. Br J Cancer, 99, 1322-9.   DOI   ScienceOn