Cancer and embryo expression protein 65 promotes cancer cell growth and metastasis

Jin,Genglin; Peng,Lirong; Zhang,Jianzhi; Qu,Like; Shou,Chengchao

doi:10.3892/ol.2015.2958

Cancer and embryo expression protein 65 promotes cancer cell growth and metastasis

Authors:
- Genglin Jin
- Lirong Peng
- Jianzhi Zhang
- Like Qu
- Chengchao Shou
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Affiliations: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China
Published online on: February 12, 2015 https://doi.org/10.3892/ol.2015.2958
Pages: 1772-1778

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Abstract

Cancer and embryo expression protein 65 (CEP65) is a centrosomal protein that is expressed at relatively high levels in embryonic tissue and different cancerous tissues, but its role in tumorigenesis remains unknown. In the present study, CEP65 was stably expressed in AGS gastric cancer cells. CEP65 was found to promote cell growth in the MTT assay and to enhance cell migration and invasion in Transwell chamber assays. To validate results from the in vitro experiments, CEP65 was stably expressed in BICR‑H1 breast cancer cells through adenovirus‑mediated transduction. By inoculating BICR‑H1 cells on chick chorioallantoic membrane (CAM), it was found that CEP65 promotes cell growth on the CAM and increases cell metastasis to the lungs of the chicken. By utilizing a xenograft severe combined immunodeficiency mouse model, CEP65 was also found to accelerate BICR‑H1 cell growth and metastasis to the lungs. Furthermore, it was shown that CEP65 increases matrix metalloproteinase (MMP)2 activity in zymographic assays, however, microarray screening and reverse transcription polymerase chain reaction validation revealed that CEP65 had no effect on the expression levels of MMP2 or MMP9, but decreased the expression levels of metastasis‑associated genes, TIMP2, RAP and VTN. Taken together, the results of the present study demonstrated the oncogenic function of CEP65 in promoting cancer cell growth and metastasis.

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1	Li J, Wang Y, Wang Z and Dong Z: Influences of amino acid sequences in FR1 region on binding activity of the scFv and Fab of an antibody to human gastric cancer cells. Immunol Lett. 71:157–165. 2000. View Article : Google Scholar : PubMed/NCBI
2	Xu G, Zhang M, Liu B, et al: Radioimmunoguided surgery in gastric cancer using 131-I labeled monoclonal antibody 3H11. Semin Surg Oncol. 10:88–94. 1994. View Article : Google Scholar : PubMed/NCBI
3	Chen DH and Shou CC: Molecular cloning of a tumor-associated antigen recognized by monoclonal antibody 3H11. Biochem Biophys Res Commun. 280:99–103. 2001. View Article : Google Scholar : PubMed/NCBI
4	Jin GL, Zhang JZ, Su R, Liu XY, Wu J, Meng L and Shou CC: Characterization of the interaction between low density lipoprotein receptor-related protein-associated protein 1 and the cancer and embryo expression protein 65. Beijing Da Xue Xue Bao. 37:297–301. 2005.(In Chinese). PubMed/NCBI
5	Sayer JA, Otto EA, O’Toole JF, Nurnberg G, Kennedy MA, Becker C, Hennies HC, Helou J, Attanasio M, Fausett BV, et al: The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4. Nat Genet. 38:674–681. 2006. View Article : Google Scholar : PubMed/NCBI
6	Guo J, Jin G, Meng L, Ma H, Nie D, Wu J, Yuan L and Shou C: Subcellullar localization of tumor-associated antigen 3H11Ag. Biochem Biophys Res Commun. 324:922–930. 2004. View Article : Google Scholar : PubMed/NCBI
7	Fukasawa K: Oncogenes and tumour suppressors take on centrosomes. Nat Rev Cancer. 7:911–924. 2007. View Article : Google Scholar
8	He TC, Zhou S, da Costa LT, Yu J, Kinzler KW and Vogelstein B: A simplified system for generating recombinant adenoviruses. Proc Natl Acad Sci USA. 95:2509–2514. 1998. View Article : Google Scholar : PubMed/NCBI
9	An P, Lei H, Zhang J, Song S, He L, Jin G, Liu X, Wu J, Meng L, Liu M and Shou C: Suppression of tumor growth and metastasis by a VEGFR-1 antagonizing peptide identified from a phage display library. Int J Cancer. 111:165–173. 2004. View Article : Google Scholar : PubMed/NCBI
10	Wang H, Wang H, Shen W, Huang H, Hu L, Ramdas L, Zhou YH, Liao WS, Fuller GN and Zhang W: Insulin-like growth factor binding protein 2 enhances glioblastoma invasion by activating invasion-enhancing genes. Cancer Res. 63:4315–4321. 2003.PubMed/NCBI
11	Hadler-Olsen E, Winberg JO and Uhlin-Hansen L: Matrix metalloproteinases in cancer: their value as diagnostic and prognostic markers and therapeutic targets. Tumour Biol. 34:2041–2051. 2013. View Article : Google Scholar : PubMed/NCBI
12	Hapke S, Kessler H, Arroyo de Prada N, Benge A, Schmitt M, Lengyel E and Reuning U: Integrin alpha(v)beta(3)/vitronectin interaction affects expression of the urokinase system in human ovarian cancer cells. J Biol Chem. 276:26340–26348. 2001. View Article : Google Scholar : PubMed/NCBI
13	Pola C, Formenti SC and Schneider RJ: Vitronectin-αvβ3 integrin engagement directs hypoxia-resistant mTOR activity and sustained protein synthesis linked to invasion by breast cancer cells. Cancer Res. 73:4571–4578. 2013. View Article : Google Scholar : PubMed/NCBI
14	Kashyap AS, Hollier BG, Manton KJ, Satyamoorthy K, Leavesley DI and Upton Z: Insulin-like growth factor-I:vitronectin complex-induced changes in gene expression effect breast cell survival and migration. Endocrinology. 152:1388–1401. 2011. View Article : Google Scholar : PubMed/NCBI
15	Chaudhary AK, Pandya S, Ghosh K and Nadkarni A: Matrix metalloproteinase and its drug targets therapy in solid and hematological malignancies: an overview. Mutat Res. 753:7–23. 2013. View Article : Google Scholar : PubMed/NCBI
16	Stetler-Stevenson WG and Seo DW: TIMP-2: an endogenous inhibitor of angiogenesis. Trends Mol Med. 11:97–103. 2005. View Article : Google Scholar : PubMed/NCBI
17	Stetler-Stevenson WG and Gavil NV: Normalization of the tumor microenvironment: evidence for tissue inhibitor of metalloproteinase-2 as a cancer therapeutic. Connect Tissue Res. 55:13–19. 2014. View Article : Google Scholar : PubMed/NCBI
18	Brand K, Baker AH, Perez-Cantó A, Possling A, Sacharjat M, Geheeb M and Arnold W: Treatment of colorectal liver metastases by adenoviral transfer of tissue inhibitor of metalloproteinases-2 into the liver tissue. Cancer Res. 60:5723–5730. 2000.PubMed/NCBI
19	Zhao YG, Xiao AZ, Park HI, Newcomer RG, Yan M, Man YG, Heffelfinger SC and Sang QX: Endometase/matrilysin-2 in human breast ductal carcinoma in situ and its inhibition by tissue inhibitors of metalloproteinases-2 and -4: a putative role in the initiation of breast cancer invasion. Cancer Res. 64:590–598. 2004. View Article : Google Scholar : PubMed/NCBI
20	Lu W, Zhou X, Hong B, Liu J and Yue Z: Suppression of invasion in human U87 glioma cells by adenovirus-mediated co-transfer of TIMP-2 and PTEN gene. Cancer Lett. 214:205–213. 2004. View Article : Google Scholar : PubMed/NCBI
21	Lee YK, So IS, Lee SC, Lee JH, Lee CW, Kim WM, Park MK, Lee ST, Park DY, Shin DY, et al: Suppression of distant pulmonary metastasis of MDA-MB 435 human breast carcinoma established in mammary fat pads of nude mice by retroviral-mediated TIMP-2 gene transfer. J Gene Med. 7:145–157. 2005. View Article : Google Scholar
22	Lin CW, Chen PN, Chen MK, Yang WE, Tang CH, Yang SF and Hsieh YS: Kaempferol reduces matrix metalloproteinase-2 expression by down-regulating ERK1/2 and the activator protein-1 signaling pathways in oral cancer cells. PLoS One. 8:e808832013. View Article : Google Scholar : PubMed/NCBI
23	Galm O, Suzuki H, Akiyama Y, Esteller M, Brock MV, Osieka R, Baylin SB and Herman JG: Inactivation of the tissue inhibitor of metalloproteinases-2 gene by promoter hypermethylation in lymphoid malignancies. Oncogene. 24:4799–4805. 2005. View Article : Google Scholar : PubMed/NCBI
24	Wang FQ, So J, Reierstad S and Fishman DA: Vascular endothelial growth factor-regulated ovarian cancer invasion and migration involves expression and activation of matrix metalloproteinases. Int J Cancer. 118:879–888. 2006. View Article : Google Scholar
25	Herz J, Hamann U, Rogne S, Myklebost O, Gausepohl H and Stanley KK: Surface location and high affinity for calcium of a 500-kd liver membrane protein closely related to the LDL-receptor suggest a physiological role as lipoprotein receptor. EMBO J. 7:4119–4127. 1988.PubMed/NCBI
26	Strickland DK, Ashcom JD, Williams S, Burgess WH, Migliorini M and Argraves WS: Sequence identity between the alpha 2-macroglobulin receptor and low density lipoprotein receptor-related protein suggests that this molecule is a multifunctional receptor. J Biol Chem. 265:17401–17404. 1990.PubMed/NCBI
27	Willnow TE, Rohlmann A, Horton J, Otani H, Braun JR, Hammer RE and Herz J: RAP, a specialized chaperone, prevents ligand-induced ER retention and degradation of LDL receptor-related endocytic receptors. EMBO J. 15:2632–2639. 1996.PubMed/NCBI
28	Bu G: Receptor-associated protein: a specialized chaperone and antagonist for members of the LDL receptor gene family. Curr Opin Lipidol. 9:149–155. 1998. View Article : Google Scholar : PubMed/NCBI
29	Herz J and Strickland DK: LRP: a multifunctional scavenger and signaling receptor. J Clin Invest. 108:779–784. 2001. View Article : Google Scholar : PubMed/NCBI
30	Yamamoto K, Troeberg L, Scilabra SD, Pelosi M, Murphy CL, Strickland DK and Nagase H: LRP-1-mediated endocytosis regulates extracellular activity of ADAMTS-5 in articular cartilage. FASEB J. 27:511–521. 2013. View Article : Google Scholar :
31	Mantuano E, Lam MS and Gonias SL: LRP1 assembles unique co-receptor systems to initiate cell signaling in response to tissue-type plasminogen activator and myelin-associated glycoprotein. J Biol Chem. 288:34009–34018. 2013. View Article : Google Scholar : PubMed/NCBI
32	Woolfson DN, Bartlett GJ, Bruning M and Thomson AR: New currency for old rope: from coiled-coil assemblies to α-helical barrels. Curr Opin Struct Biol. 22:432–441. 2012. View Article : Google Scholar : PubMed/NCBI
33	Koyanagi M, Hijikata M, Watashi K, Masui O and Shimotohno K: Centrosomal P4.1-associated protein is a new member of transcriptional coactivators for nuclear factor-kappaB. J Biol Chem. 280:12430–12437. 2005. View Article : Google Scholar : PubMed/NCBI