Zinc finger protein 185 is a liver metastasis‑associated factor in colon cancer patients

Furukawa,Daisuke; Chijiwa,Tsuyoshi; Matsuyama,Masahiro; Mukai,Masaya; Matsuo,Ei-ichi; Nishimura,Osamu; Kawai,Kenji; Suemizu,Hiroshi; Hiraoka,Nobuyoshi; Nakagohri,Toshio; Yasuda,Seiei; Nakamura,Masato

doi:10.3892/mco.2014.298

Zinc finger protein 185 is a liver metastasis‑associated factor in colon cancer patients

Authors:
- Daisuke Furukawa
- Tsuyoshi Chijiwa
- Masahiro Matsuyama
- Masaya Mukai
- Ei-ichi Matsuo
- Osamu Nishimura
- Kenji Kawai
- Hiroshi Suemizu
- Nobuyoshi Hiraoka
- Toshio Nakagohri
- Seiei Yasuda
- Masato Nakamura
View Affiliations

Affiliations: Department of Surgery, Tokai University School of Medicine, Isehara, Kanagawa259‑1193, Japan, Laboratory Animal Research Department, Central Institute for Experimental Animals, Kawasaki, Kanagawa 210‑0821, Japan, Department of Surgery, Tokai University School of Medicine, Isehara, Kanagawa 259‑1193, Japan, Global Application Development Center, Analytical and Measuring Instruments Division, Shimadzu Corporation, Kyoto 604‑8511, Japan, The Integrated Center for Mass Spectrometry, Graduate School of Medicine, Kobe University, Kobe, Hyogo 650‑0017, Japan, Pathological Analysis Center, Central Institute for Experimental Animals, Kawasaki, Kanagawa 210‑0821, Japan, Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo 104‑0045, Japan, Department of Regenerative Medicine, Tokai University School of Medicine, Isehara, Kanagawa 259‑1193, Japan
Published online on: May 29, 2014 https://doi.org/10.3892/mco.2014.298
Pages: 709-713

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

LIM domain proteins are involved in several fundamental biological processes, including cell lineage specification, cytoskeleton organization and organ development. Zinc finger protein 185 (ZNF185) is one of the LIM domain proteins considered to be involved in the regulation of cellular differentiation and/or proliferation. However, the detailed functions and properties of ZNF185 in the multistep process of cancer biology have not yet been elucidated. In this study, we analyzed the association between ZNF185 and the clinicopathological characteristics of colon cancer, such as patient age and gender, histological type, lymphatic and venous involvement, T and N status, liver metastasis and stage. ZNF185 protein expression was immunohistochemically analyzed and ZNF185 was detected in the cancer cells of 78 of the 87 colon cancer patients. The correlation between ZNF185 and histological type was significant (P=0.010, G-test). ZNF185 expression was also significantly correlated with liver metastasis (P=0.030, G-test). A multivariate analysis using the Cox proportional hazards model was performed among cause-specific survival rate, ZNF185 expression and clinicopathological characteristics. histological type, liver metastasis and ZNF185 expression were found to be independent prognostic indicators (P=0.028, P<0.0001 and P=0.036, respectively). Therefore, ZNF185 expression was found to be an independent indicator of liver metastasis and prognosis in patients with colon cancer.

View Figures

View References

1	Jemal A, Siegel R, Ward E, et al: Cancer statistics, 2008. CA Cancer J Clin. 58:71–96. 2008. View Article : Google Scholar
2	Sadahiro S, Suzuki T, Ishikawa K, et al: Recurrence patterns after curative resection of colorectal cancer in patients followed for a minimum of ten years. Hepatogastroenterology. 50:1362–1366. 2003.PubMed/NCBI
3	Yamada H, Hirano S, Tanaka E, Shichinohe T and Kondo S: Surgical treatment of liver metastases from pancreatic cancer. HPB (Oxford). 8:85–88. 2006. View Article : Google Scholar : PubMed/NCBI
4	Suemizu H, Monnai M, Ohnishi Y, Ito M, Tamaoki N and Nakamura M: Identification of a key molecular regulator of liver metastasis in human pancreatic carcinoma using a novel quantitative model of metastasis in NOD/SCID/gammacnull (NOG) mice. Int J Oncol. 31:741–751. 2007.PubMed/NCBI
5	Hamada K, Monnai M, Kawai K, et al: Liver metastasis models of colon cancer for evaluation of drug efficacy using NOD/Shi-scid IL2Rgammanull (NOG) mice. Int J Oncol. 32:153–159. 2008.PubMed/NCBI
6	Matsuyama M, Wakui M, Monnai M, et al: Reduced CD73 expression and its association with altered purine nucleotide metabolism in colorectal cancer cells robustly causing liver metastases. Oncol Lett. 1:431–436. 2010.
7	Matsuo E, Watanabe M, Kuyama H and Nishimura O: A new strategy for protein biomarker discovery utilizing 2-nitrobenzenesulfenyl (NBS) reagent and its applications to clinical samples. J Chromatogr B Analyt Technol Biomed Life Sci. 877:2607–2614. 2009. View Article : Google Scholar : PubMed/NCBI
8	Way JC and Chalfie M: mec-3, a homeobox-containing gene that specifies differentiation of the touch receptor neurons in C. elegans. Cell. 54:5–16. 1988. View Article : Google Scholar : PubMed/NCBI
9	Freyd G, Kim SK and Horvitz HR: Novel cysteine-rich motif and homeodomain in the product of the Caenorhabditis elegans cell lineage gene lin-11. Nature. 344:876–879. 1990. View Article : Google Scholar : PubMed/NCBI
10	Karlsson O, Thor S, Norberg T, Ohlsson H and Edlund T: Insulin gene enhancer binding protein Isl-1 is a member of a novel class of proteins containing both a homeo- and a Cys-His domain. Nature. 344:879–882. 1990. View Article : Google Scholar : PubMed/NCBI
11	Dawid IB, Breen JJ and Toyama R: LIM domains: multiple roles as adapters and functional modifiers in protein interactions. Trends Genet. 14:156–162. 1998. View Article : Google Scholar : PubMed/NCBI
12	Zheng Q and Zhao Y: The diverse biofunctions of LIM domain proteins: determined by subcellular localization and protein-protein interaction. Biol Cell. 99:489–502. 2007. View Article : Google Scholar : PubMed/NCBI
13	Pérez-Alvarado GC, Miles C, Michelsen JW, et al: Structure of the carboxy-terminal LIM domain from the cysteine rich protein CRP. Nat Struct Biol. 1:388–398. 1994.PubMed/NCBI
14	Schmeichel KL and Beckerle MC: The LIM domain is a modular protein-binding interface. Cell. 79:211–219. 1994. View Article : Google Scholar : PubMed/NCBI
15	Heiss NS, Gloeckner G, Bächner D, et al: Genomic structure of a novel LIM domain gene (ZNF185) in Xq28 and comparisons with the orthologous murine transcript. Genomics. 43:329–338. 1997. View Article : Google Scholar : PubMed/NCBI
16	Vanaja DK, Cheville JC, Iturria SJ and Young CY: Transcriptional silencing of zinc finger protein 185 identified by expression profiling is associated with prostate cancer progression. Cancer Res. 63:3877–3882. 2003.PubMed/NCBI
17	Zhang JS, Gong A and Young CY: ZNF185, an actin-cytoskeleton-associated growth inhibitory LIM protein in prostate cancer. Oncogene. 26:111–122. 2007. View Article : Google Scholar : PubMed/NCBI
18	Maul RS and Chang DD: EPLIN, epithelial protein lost in neoplasm. Oncogene. 18:7838–7841. 1999. View Article : Google Scholar : PubMed/NCBI
19	Tatarelli C, Linnenbach A, Mimori K and Croce CM: Characterization of the human TESTIN gene localized in the FRA7G region at 7q31.2. Genomics. 68:1–12. 2000. View Article : Google Scholar : PubMed/NCBI
20	Tobias ES, Hurlstone AF, MacKenzie E, McFarlane R and Black DM: The TES gene at 7q31.1 is methylated in tumours and encodes a novel growth-suppressing LIM domain protein. Oncogene. 20:2844–2853. 2001. View Article : Google Scholar : PubMed/NCBI
21	Visvader JE, Venter D, Hahm K, et al: The LIM domain gene LMO4 inhibits differentiation of mammary epithelial cells in vitro and is overexpressed in breast cancer. Proc Natl Acad Sci USA. 98:14452–14457. 2001. View Article : Google Scholar : PubMed/NCBI
22	Song Y, Maul RS, Gerbin CS and Chang DD: Inhibition of anchorage-independent growth of transformed NIH3T3 cells by epithelial protein lost in neoplasm (EPLIN) requires localization of EPLIN to actin cytoskeleton. Mol Biol Cell. 13:1408–1416. 2002. View Article : Google Scholar : PubMed/NCBI
23	Sum EY, Peng B, Yu X, et al: The LIM domain protein LMO4 interacts with the cofactor CtIP and the tumor suppressor BRCA1 and inhibits BRCA1 activity. J Biol Chem. 277:7849–7856. 2002. View Article : Google Scholar : PubMed/NCBI
24	Garvalov BK, Higgins TE, Sutherland JD, et al: The conformational state of Tes regulates its zyxin-dependent recruitment to focal adhesions. J Cell Biol. 161:33–39. 2003. View Article : Google Scholar : PubMed/NCBI
25	Wang B, Feng P, Xiao Z and Ren EC: LIM and SH3 protein 1 (Lasp1) is a novel p53 transcriptional target involved in hepatocellular carcinoma. J Hepatol. 50:528–537. 2009. View Article : Google Scholar : PubMed/NCBI
26	Grunewald TG, Kammerer U, Schulze E, et al: Silencing of LASP-1 influences zyxin localization, inhibits proliferation and reduces migration in breast cancer cells. Exp Cell Res. 312:974–982. 2006. View Article : Google Scholar : PubMed/NCBI
27	Grunewald TG, Kammerer U, Winkler C, et al: Overexpression of LASP-1 mediates migration and proliferation of human ovarian cancer cells and influences zyxin localisation. Br J Cancer. 96:296–305. 2007. View Article : Google Scholar : PubMed/NCBI
28	Gonzalez HE, Gujrati M, Frederick M, et al: Identification of 9 genes differentially expressed in head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 129:754–759. 2003. View Article : Google Scholar : PubMed/NCBI
29	Medina PP, Carretero J, Ballestar E, et al: Transcriptional targets of the chromatin-remodelling factor SMARCA4/BRG1 in lung cancer cells. Hum Mol Genet. 14:973–982. 2005. View Article : Google Scholar : PubMed/NCBI
30	Taira M, Evrard JL, Steinmetz A and Dawid IB: Classification of LIM proteins. Trends Genet. 11:431–432. 1995. View Article : Google Scholar : PubMed/NCBI
31	Benson AB III, Schrag D, Somerfield MR, et al: American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol. 22:3408–3419. 2004. View Article : Google Scholar : PubMed/NCBI
32	Staib L, Link KH, Blatz A and Beger HG: Surgery of colorectal cancer: surgical morbidity and five- and ten-year results in 2400 patients - monoinstitutional experience. World J Surg. 26:59–66. 2002.PubMed/NCBI
33	Schiffmann L, Eiken AK, Gock M and Klar E: Is the lymph node ratio superior to the Union for International Cancer Control (UICC) TNM system in prognosis of colon cancer? World J Surg Oncol. 11:792013. View Article : Google Scholar : PubMed/NCBI
34	Sadahiro S, Suzuki T, Tanaka A, Okada K and Kamata H: Hematogenous metastatic patterns of curatively resected colon cancer were different from those of stage IV and autopsy cases. Jpn J Clin Oncol. 43:444–447. 2013. View Article : Google Scholar : PubMed/NCBI
35	Baba H, Watanabe M, Okabe H, et al: Upregulation of ERCC1 and DPD expressions after oxaliplatin-based first-line chemotherapy for metastatic colorectal cancer. Br J Cancer. 107:1950–1955. 2012. View Article : Google Scholar : PubMed/NCBI