microRNA-18b is upregulated in breast cancer and modulates genes involved in cell migration

Fonseca-Sanchéz,Miguel  A.; Pérez-Plasencia,Carlos; Fernández-Retana,Jorge; Arechaga-Ocampo,Elena; Marchat,Laurence  A.; Rodríguez-Cuevas,Sergio; Bautista-Piña,Veronica; Arellano-Anaya,Zaira  E.; Flores-Pérez,Ali; Diaz-Chávez,José; López-Camarillo,César

doi:10.3892/or.2013.2691

microRNA-18b is upregulated in breast cancer and modulates genes involved in cell migration

Authors:
- Miguel A. Fonseca-Sanchéz
- Carlos Pérez-Plasencia
- Jorge Fernández-Retana
- Elena Arechaga-Ocampo
- Laurence A. Marchat
- Sergio Rodríguez-Cuevas
- Veronica Bautista-Piña
- Zaira E. Arellano-Anaya
- Ali Flores-Pérez
- José Diaz-Chávez
- César López-Camarillo
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Affiliations: Oncogenomics and Cancer Proteomics Laboratory, Genomics Sciences Program, Autonomous University of Mexico City, Mexico City, Mexico, Oncogenomics Laboratory, National Institute of Cancerology, Mexico City, Mexico, Virus and Cancer Laboratory, National Institute of Cancerology, Mexico City, Mexico, Molecular Biomedicine Program and Biotechnology Network, National School of Medicine and Homeopathy, National Polytechnic Institute, Mexico City, Mexico, Institute of Breast Diseases-FUCAM, Mexico City, Mexico, Unit of Biomedical Research in Cancer, Institute of Biomedical Research, UNAM/National Cancer Institute, Mexico City, Mexico
Published online on: August 22, 2013 https://doi.org/10.3892/or.2013.2691
Pages: 2399-2410

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Abstract

microRNAs are small non-coding RNAs of ~22 nucleotides that function at post-transcriptional level as negative regulators of gene expression. Aberrant expression of microRNAs could promote uncontrolled proliferation, migration and invasion of human cancer cells. In this study, we analyzed the expression of microRNA-18b (miR-18b) in breast cancer cell lines and in a set of clinical specimens. Our results showed that miR-18b was upregulated in four out of five breast cancer cell lines and also in breast tumors. In order to identify potential gene targets, we carried out transcriptional profiling of MDA-MB-231 breast cancer cells that ectopically expressed miR-18b. Our results showed that 263 genes were significantly modulated in miR-18b-deficient cells (fold change >1.5; P≤0.05). We found that knock-down of miR-18b induced the upregulation of 55 olfactory receptor (OR) genes and nine genes (NLRP7, KLK3, OLFM3, POSTN, MAGED4B, KIR3DL3, CRX, SEMG1 and CEACAM5) with key roles in cell migration and metastasis. Consistently, we found that ectopic inhibition of miR-18b suppressed the migration of two breast cancer cell models in vitro. In conclusion, we have uncovered genes directly or indirectly modulated by miR-18b which may represent potential therapeutic targets in breast cancer. Our data also pointed out a role of miR-18b in migration of breast cancer cells.

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1	Hammond SM: RNAi, microRNAs, and human disease. Cancer Chemother Pharmacol. 58:S63–S68. 2006. View Article : Google Scholar : PubMed/NCBI
2	Tanzer A and Stadler PF: Molecular evolution of a microRNA cluster. J Mol Biol. 339:327–335. 2004. View Article : Google Scholar : PubMed/NCBI
3	Mendell JT: miRiad roles for the miR-17-92 cluster in development and disease. Cell. 133:217–222. 2008. View Article : Google Scholar : PubMed/NCBI
4	Ventura A, Young AG, Winslow MM, Lintault L, Meissner A, Erkeland SJ, Newman J, Bronson RT, Crowley D, Stone JR, Jaenisch R, Sharp PA and Jacks T: Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell. 132:875–886. 2008. View Article : Google Scholar : PubMed/NCBI
5	Tatsuguchi M, Seok HY, Callis TE, Thomson JM, Chen JF, Newman M, Rojas M, Hammond SM and Wang DZ: Expression of microRNAs is dynamically regulated during cardiomyocyte hypertrophy. J Mol Cell Cardiol. 42:1137–1141. 2007. View Article : Google Scholar : PubMed/NCBI
6	Otaegui D, Baranzini SE, Armañanzas R, Calvo B, Muñoz-Culla M, Khankhanian P, Inza I, Lozano JA, Castillo-Triviño T, Asensio A, Olaskoaga J and López de Munain A: Differential micro RNA expression in PBMC from múltiple sclerosis patients. PloS One. 4:e63092009.PubMed/NCBI
7	Zhang ZZ, Liu X, Wang DQ, Teng MK, Niu LW, Huang AL and Liang Z: Hepatitis B virus and hepatocellular carcinoma at the miRNA level. World J Gastroenterol. 17:3353–3358. 2011. View Article : Google Scholar : PubMed/NCBI
8	Guo J, Miao Y, Xiao B, Huan R, Jiang Z, Meng D and Wang Y: Differential expression of microRNA species in human gastric cancer versus non-tumorous tissues. J Gastroenterol Hepatol. 24:652–657. 2009. View Article : Google Scholar : PubMed/NCBI
9	Kim TH, Kim YK, Kwon Y, Heo JH, Kang H, Kim G and An HJ: Deregulation of miR-519a, 153, and 485-5p and its clinicopathological relevance in ovarian epithelial tumours. Histopathology. 57:734–743. 2010. View Article : Google Scholar : PubMed/NCBI
10	Sand M, Skrygan M, Sand D, Georgas D, Hahn SA, Gambichler T, Altmeyer P and Bechara FG: Expression of microRNAs in basal cell carcinoma. Br J Dermatol. 167:847–855. 2012. View Article : Google Scholar : PubMed/NCBI
11	Wang YX, Zhang XY, Zhang BF, Yang CQ, Chen XM and Gao HJ: Initial study of microRNA expression profiles of colonic cancer without lymph node metastasis. J Dig Dis. 11:50–54. 2010. View Article : Google Scholar : PubMed/NCBI
12	He X, DiMeco F, Vescovi A, Heth J, Muraszko K and Fan X: MIR-18b regulates glioblastoma neurosphere growth through NOTCH2, NEDD9, and MEKK1. Neuro Oncol. 14(Suppl 6): vi142–vi152. 2012.
13	Leivonen SK, Mäkelä R, Ostling P, Kohonen P, Haapa-Paananen S, Kleivi K, Enerly E, Aakula A, Hellström K, Sahlberg N, Kristensen VN, Børresen-Dale AL, Saviranta P, Perälä M and Kallioniemi O: Protein lysate microarray analysis to identify microRNAs regulating estrogen receptor signaling in breast cancer cell lines. Oncogene. 28:3926–3936. 2009. View Article : Google Scholar : PubMed/NCBI
14	Yoshimoto N, Toyama T, Takahashi S, Sugiura H, Endo Y, Iwasa M, Fujii Y and Yamashita H: Distinct expressions of microRNAs that directly target estrogen receptor α in human breast cancer. Breast Cancer Res Treat. 130:331–339. 2011.PubMed/NCBI
15	Cookson VJ, Bentley MA, Hogan BV, Horgan K, Hayward BE, Hazelwood LD and Hughes TA: Circulating microRNA profiles reflect the presence of breast tumours but not the profiles of microRNA within the tumours. Cell Oncol. 35:301–308. 2012. View Article : Google Scholar : PubMed/NCBI
16	Simon A and Biot E: ANAIS: Analysis of NimbleGen arrays interface. Bioinformatics. 26:2468–2469. 2010. View Article : Google Scholar : PubMed/NCBI
17	Kang N and Koo J: Olfactory receptors in non-chemosensory tissues. BMB Rep. 5:612–622. 2012. View Article : Google Scholar
18	Neuhaus EM, Zhang W, Gelis L, Deng Y, Noldus J and Hatt H: Activation of an olfactory receptor inhibits proliferation of prostate cancer cells. J Biol Chem. 284:16218–16225. 2009. View Article : Google Scholar : PubMed/NCBI
19	Zhang W, Edwards A, Fan W, Flemington EK and Zhang K: miRNA-mRNA correlation-network modules in human prostate cancer and the differences between primary and metastatic tumor subtypes. PLoS One. 7:e401302012. View Article : Google Scholar : PubMed/NCBI
20	Betel D, Wilson M, Gabow A, Marks DS and Sander C: The microRNA.org resource: targets and expression. Nucleic Acids Res. 36:149–153. 2008.PubMed/NCBI
21	Plessy C, Pascarella G, Bertin N, Akalin A, Carrieri C, Vassalli A, Lazarevic D, Severin J, Vlachouli C, Simone R, Faulkner GJ, Kawai J, Daub CO, Zucchelli S, Hayashizaki Y, Mombaerts P, Lenhard B, Gustincich S and Carninci P: Promoter architecture of mouse olfactory receptor genes. Genome Res. 22:486–497. 2012. View Article : Google Scholar : PubMed/NCBI
22	Clements J, Ward G, Kaushal A, Hi SI, Kennett C and Nicol D: A prostate-specific antigen-like protein associated with renal cell carcinoma in women. Clin Cancer Res. 3:1427–1431. 1997.PubMed/NCBI
23	Majumdar S and Diamandis EP: The promoter and the enhancer region of the KLK3 (prostate specific antigen) gene is frequently mutated in breast tumours and in breast carcinoma cell lines. Br J Cancer. 79:1594–1602. 1999. View Article : Google Scholar : PubMed/NCBI
24	Takeshita S, Kikuno R, Tezuka K and Amann E: Osteoblast-specific factor 2: cloning of a putative bone adhesion protein with homology with the insect protein fasciclin I. Biochem J. 15:271–278. 1993.PubMed/NCBI
25	Horiuchi K, Amizuka N, Takeshita S, Takamatsu H, Katsuura M, Ozawa H, Toyama Y, Bonewald LF and Kudo A: Identification and characterization of a novel protein, periostin, with restricted expression to periosteum and periodontal ligament and increased expression by transforming growth factor beta. J Bone Miner Res. 14:1239–1249. 1999. View Article : Google Scholar : PubMed/NCBI
26	Siriwardena BS, Kudo Y, Ogawa I, Kitagawa M, Kitajima S, Hatano H, Tilakaratne WM, Miyauchi M and Takata T: Periostin is frequently overexpressed and enhances invasion and angiogenesis in oral cancer. Br J Cancer. 95:1396–1403. 2006. View Article : Google Scholar : PubMed/NCBI
27	Jonsdottir K, Janssen SR, Da Rosa FC, Gudlaugsson E, Skaland I, Baak JP and Janssen EA: Validation of expression patterns for nine miRNAs in 204 lymph-node negative breast cancers. PLoS One. 7:e486922012. View Article : Google Scholar : PubMed/NCBI
28	Fornier M and Fumoleau P: The paradox of triple negative breast cancer: novel approaches to treatment. Breast J. 1:41–51. 2012. View Article : Google Scholar : PubMed/NCBI
29	Dreyer WJ: The area code hypothesis revisited: olfactory receptors and other related transmembrane receptors may function as the last digits in a cell surface code for assembling embryos. Proc Natl Acad Sci USA. 95:9072–9077. 1998. View Article : Google Scholar
30	Goto T, Salpekar A and Monk M: Expression of a testis-specific member of the olfactory receptor gene family in human primordial germ cells. Mol Hum Reprod. 7:553–558. 2001. View Article : Google Scholar : PubMed/NCBI
31	Weng J, Wang J, Hu X, Wang F, Ittmann M and Liu M: PSGR2, a novel G-protein coupled receptor, is overexpressed in human prostate cancer. Int J Cancer. 118:1471–1480. 2006. View Article : Google Scholar : PubMed/NCBI
32	McIntyre A, Summersgill B, Jafer O, Rodriguez S, Zafarana G, Oosterhuis JW, Gillis AJ, Looijenga L, Cooper C, Huddart R, Clark J and Shipley J: Defining minimum genomic regions of imbalance involved in testicular germ cell tumors of adolescents and adults through genome wide microarray analysis of cDNA clones. Oncogene. 23:9142–9147. 2004. View Article : Google Scholar : PubMed/NCBI
33	Raish M, Khurshid M, Ansari MA, Chaturvedi PK, Bae SM, Kim JH, Park EK, Park DC and Ahn WS: Analysis of molecular cytogenetic alterations in uterine leiomyosarcoma by array-based comparative genomic hybridization. J Cancer Res Clin Oncol. 138:1173–1186. 2012. View Article : Google Scholar : PubMed/NCBI
34	Muranen TA, Greco D, Fagerholm R, et al: Breast tumors from CHEK2 110delC-mutation carriers: genomic landscape and clinical implications. Breast Cancer Res. 13:R902011. View Article : Google Scholar : PubMed/NCBI
35	Wescott MP, Rovira M, Reichert M, von Burstin J, Means A, Leach SD and Rustgi AK: Pancreatic ductal morphogenesis and the Pdx1 homeodomain transcription factor. Mol Biol Cell. 20:4838–4844. 2009. View Article : Google Scholar : PubMed/NCBI
36	Sakai H, Eishi Y, Li XL, Akiyama Y, Miyake S, Takizawa T, Konishi N, Tatematsu M, Koike M and Yuasa Y: PDX1 homeobox protein expression in pseudopyloric glands and gastric carcinomas. Gut. 53:323–330. 2004. View Article : Google Scholar : PubMed/NCBI
37	Ma J, Chen M, Wang J, Xia HH, Zhu S, Liang Y, Gu Q, Qiao L, Dai Y, Zou B, Li Z, Zhang Y, Lan H and Wong BC: Pancreatic duodenal homeobox-1 (PDX1) functions as a tumor suppressor in gastric cancer. Carcinogenesis. 29:1327–1333. 2008. View Article : Google Scholar : PubMed/NCBI
38	Galmiche L, Sarnacki S, Verkarre V, Boizet B, Duvillie B, Fabre M and Jaubert F: Transcription factors involved in pancreas development are expressed in paediatric solid pseudopapillary tumours. Histopathology. 53:318–324. 2008. View Article : Google Scholar : PubMed/NCBI
39	Park JY, Hong SM, Klimstra DS, Goggins MG, Maitra A and Hruban RH: Pdx1 expression in pancreatic precursor lesions and neoplasms. Appl Immunohistochem Mol Morphol. 19:444–449. 2011. View Article : Google Scholar : PubMed/NCBI
40	Nakata T, Kitamura Y, Shimizu K, Tanaka S, Fujimori M, Yokoyama S, Ito K and Emi M: Fusion of a novel gene, ELKS, to RET due to translocation t(10;12)(q11;p13) in a papillary thyroid carcinoma. Genes Chromosomes Cancer. 25:97–103. 1999. View Article : Google Scholar : PubMed/NCBI
41	Bakker AB, Phillips JH, Figdor CG and Lanier LL: Killer cell inhibitory receptors for MHC class I molecules regulate lysis of melanoma cells mediated by NK cells, gamma delta T cells, and antigen-specific CTL. J Immunol. 160:5239–5245. 1998.PubMed/NCBI
42	Maat W, van der Slik AR, Verhoeven DH, Alizadeh BZ, Ly LV, Verduijn W, Luyten GP, Mulder A, van Hall T, Koning F, Jager MJ and van Bergen J: Evidence for natural killer cell-mediated protection from metastasis formation in uveal melanoma patients. Invest Ophthalmol Vis Sci. 50:2888–2895. 2009. View Article : Google Scholar : PubMed/NCBI
43	Okada K, Hirota E, Mizutani Y, Fujioka T, Shuin T, Miki T, Nakamura Y and Katagiri T: Oncogenic role of NALP7 in testicular seminomas. Cancer Sci. 95:949–954. 2004. View Article : Google Scholar : PubMed/NCBI
44	Ohno S, Kinoshita T, Ohno Y, Minamoto T, Suzuki N, Inoue M and Suda T: Expression of NLRP7 (PYPAF3, NALP7) protein in endometrial cancer tissues. Anticancer Res. 28:2493–2498. 2008.PubMed/NCBI
45	Coma M, Vicente R, Busquets S, Carbó N, Tamkun MM, López-Soriano FJ, Argilés JM and Felipe A: Impaired voltage-gated K⁺ channel expression in brain during experimental cancer cachexia. FEBS Lett. 536:45–50. 2003.
46	Usami S, Motoyama S, Koyota S, Wang J, Hayashi-Shibuya K, Maruyama K, Takahashi N, Saito H, Minamiya Y, Takasawa S, Ogawa J and Sugiyama T: Regenerating gene I regulates interleukin-6 production in squamous esophageal cancer cells. Biochem Biophys Res Commun. 29:4–8. 2010. View Article : Google Scholar : PubMed/NCBI
47	Hayashi K, Motoyama S, Koyota S, Koizumi Y, Wang J, Takasawa S, Itaya-Hironaka A, Sakuramoto-Tsuchida S, Maruyama K, Saito H, Minamiya Y, Ogawa J and Sugiyama T: REG I enhances chemo- and radiosensitivity in squamous cell esophageal cancer cells. Cancer Sci. 99:2491–2495. 2008. View Article : Google Scholar : PubMed/NCBI
48	Wiśniewski A, Jankowska R, Passowicz-Muszyńska E, Wiśniewska E, Majorczyk E, Nowak I, Frydecka I and Kuśnierczyk P: KIR2DL2/S2 and HLA-C C1C1 genotype is associated with better response to treatment and prolonged survival of patients with non-small cell lung cancer in a Polish Caucasian population. Hum Immunol. 73:927–931. 2012.PubMed/NCBI
49	Almalte Z, Samarani S, Iannello A, Debbeche O, Duval M, Infante-Rivard C, Amre DK, Sinnett D and Ahmad A: Novel associations between activating killer-cell immunoglobulin-like receptor genes and childhood leukemia. Blood. 118:1323–1328. 2011. View Article : Google Scholar : PubMed/NCBI
50	Cumming AP, Hopmans SN, Vukmirović-Popović S and Duivenvoorden WC: PSA affects prostate cancer cell invasion in vitro and induces an osteoblastic phenotype in bone in vivo. Prostate Cancer Prostatic Dis. 14:286–294. 2011. View Article : Google Scholar : PubMed/NCBI
51	Mattsson JM, Närvänen A, Stenman UH and Koistinen H: Peptides binding to prostate-specific antigen enhances its antiangiogenic activity. Prostate. 72:1588–1594. 2012. View Article : Google Scholar : PubMed/NCBI
52	Saxena P, Trerotola M, Wang T, Li J, Sayeed A, Vanoudenhove J, Adams DS, Fitzgerald TJ, Altieri DC and Languino LR: PSA regulates androgen receptor expression in prostate cancer cells. Prostate. 72:769–776. 2012. View Article : Google Scholar : PubMed/NCBI
53	O'Mara TA, Nagle CM, Batra J, Kedda MA, Clements JA and Spurdle AB: Kallikrein-related peptidase 3 (KLK3/PSA) single nucleotide polymorphisms and ovarían cancer survival. Twin Res Hum Genet. 14:323–327. 2011.PubMed/NCBI
54	Black MH and Diamandis EP: The diagnostic and prognostic utility of prostate-specific antigen for diseases of the breast. Breast Cancer Res Treat. 59:1–14. 2000. View Article : Google Scholar : PubMed/NCBI
55	Szczepanski MJ, DeLeo AB, Łuczak M, Molinska-Glura M, Misiak J, Szarzynska B, Dworacki G, Zagor M, Rozwadowska N, Kurpisz M, Krzeski A, Kruk-Zagajewska A, Kopec T, Banaszewski J and Whiteside TL: PRAME expression in head and neck cancer correlates with markers of poor prognosis and might help in selecting candidates for retinoid chemoprevention in pre-malignant lesions. Oral Oncol. 49:144–151. 2012. View Article : Google Scholar : PubMed/NCBI
56	Español AJ and Sales MN: Different muscarinic receptors are involved in the proliferation of murine mammary adenocarcinoma cell lines. Int J Mol Med. 13:311–317. 2004.PubMed/NCBI
57	Fiszman GL, Middonno MC, de la Torre E, Farina M, Español AJ and Sales ME: Activation of muscarinic cholinergic receptors induces MCF-7 cells proliferation and angiogenesis by stimulating nitric oxide synthase activity. Cancer Biol Ther. 6:1106–1113. 2007. View Article : Google Scholar
58	Español AJ, de la Torre E, Fiszman GL and Sales ME: Role of non-neuronal cholinergic system in breast cancer progression. Life Sci. 80:2281–2285. 2007.PubMed/NCBI
59	Ferretti M, Fabbiano C, Di Bari M, Ponti D, Calogero A and Tata AM: M2 muscarinic receptors inhibit cell proliferation in human glioblastoma cell lines. Life Sci. 91:1134–1137. 2012. View Article : Google Scholar : PubMed/NCBI
60	Cabadak H, Aydin B and Kan B: Regulation of M2, M3, and M4 muscarinic receptor expression in K562 chronic myelogenous leukemic cells by carbachol. J Recept Signal Transduct Res. 31:26–32. 2011. View Article : Google Scholar : PubMed/NCBI
61	Keenan J, Joyce H, Aherne S, O'Dea S, Doolan P, Lynch V and Clynes M: Olfactomedin III expression contributes to anoikis-resistance in clonal variants of a human lung squamous carcinoma cell line. Exp Cell Res. 318:593–602. 2012. View Article : Google Scholar : PubMed/NCBI
62	Miljkovic-Licina M, Hammel P, Garrido-Urbani S, Lee BP, Meguenani M, Chaabane C, Bochaton-Piallat ML and Imhof BA: Targeting olfactomedin-like 3 inhibits tumor growth by impairing angiogenesis and pericyte coverage. Mol Cancer Ther. 11:2588–2599. 2012. View Article : Google Scholar : PubMed/NCBI
63	Rouget-Quermalet V, Giustiniani J, Marie-Cardine A, Beaud G, Besnard F, Loyaux D, Ferrara P, Leroy K, Shimizu N, Gaulard P, Bensussan A and Schmitt C: Protocadherin 15 (PCDH15): a new secreted isoform and a potential marker for NK/T cell lymphomas. Oncogene. 25:2807–2811. 2006. View Article : Google Scholar : PubMed/NCBI
64	Adachi K, Toyota M, Sasaki Y, Yamashita T, Ishida S, Ohe-Toyota M, Maruyama R, Hinoda Y, Saito T, Imai K, Kudo R and Tokino T: Identification of SCN3B as a novel p53-inducible proapoptotic gene. Oncogene. 23:7791–7798. 2004. View Article : Google Scholar : PubMed/NCBI
65	Rodrigues RG, Panizo-Santos A, Cashel JA, Krutzsch HC, Merino MJ and Roberts DD: Semenogelins are ectopically expressed in small cell lung carcinoma. Clin Cancer Res. 7:854–860. 2001.PubMed/NCBI
66	Zhang Y, Wang Z, Zhang J, Farmer B and Lim SH: Semenogelin I expression in myeloma cells can be upregulated pharmacologically. Leuk Res. 32:1889–1894. 2008. View Article : Google Scholar : PubMed/NCBI
67	Hienonen T, Sammalkorpi H, Enholm S, Alhopuro P, Barber TD, Lehtonen R, Nupponen NN, Lehtonen H, Salovaara R, Mecklin JP, Järvinen H, Koistinen R, Arango D, Launonen V, Vogelstein B, Karhu A and Aaltonen LA: Mutations in two short noncoding mononucleotide repeats in most microsatellite-unstable colorectal cancers. Cancer Res. 65:4607–4613. 2005. View Article : Google Scholar : PubMed/NCBI
68	Mitra A, Richardson RT and O'Rand MG: Analysis of recombinant human semenogelin as an inhibitor of human sperm motility. Biol Reprod. 82:489–496. 2010. View Article : Google Scholar : PubMed/NCBI
69	Canacci AM, Izumi K, Zheng Y, Gordetsky J, Yao JL and Miyamoto H: Expression of semenogelins I and II and its prognostic significance in human prostate cancer. Prostate. 71:1108–1114. 2011. View Article : Google Scholar : PubMed/NCBI
70	Santagata S, Maire CL, Idbaih A, Geffers L, Correll M, Holton K, Quackenbush J and Ligon KL: CRX is a diagnostic marker of retinal and pineal lineage tumors. PLoS One. 4:e79322009. View Article : Google Scholar : PubMed/NCBI
71	Glubrecht DD, Kim JH, Russell L, Bamforth JS and Godbout R: Differential CRX and OTX2 expression in human retina and retinoblastoma. J Neurochem. 111:250–263. 2009. View Article : Google Scholar : PubMed/NCBI
72	Terry J, Calicchio ML, Rodriguez-Galindo C and Perez-Atayde AR: Immunohistochemical expression of CRX in extracranial malignant small round cell tumors. Am J Surg Pathol. 36:1165–1169. 2012. View Article : Google Scholar : PubMed/NCBI
73	Yousef GM, Scorilas A, Jung K, Ashworth LK and Diamandis EP: Molecular cloning of the human kallikrein 15 gene (KLK15). J Biol Chem. 276:53–61. 2001. View Article : Google Scholar : PubMed/NCBI
74	Yousef GM, Scorilas A, Katsaros D, Fracchioli S, Iskander L, Borgono C, Rigault de la Longrais IA, Puopolo M, Massobrio M and Diamandis EP: Prognostic value of the human kallikrein gene 15 expression in ovarian cancer. J Clin Oncol. 21:3119–3126. 2003. View Article : Google Scholar : PubMed/NCBI
75	Rabien A, Fritzsche FR, Jung M, Tölle A, Diamandis EP, Miller K, Jung K, Kristiansen G and Stephan C: KLK15 is a prognostic marker for progression-free survival in patients with radical prostatectomy. Int J Cancer. 127:2386–2394. 2010. View Article : Google Scholar : PubMed/NCBI
76	Yousef GM, Scorilas A, Magklara A, Memari N, Ponzone R, Sismondi P, Biglia N, Abd Ellatif M and Diamandis EP: The androgen-regulated gene human kallikrein 15 (KLK15) is an indpendent and favourable prognostic marker for breast cancer. Br J Cancer. 87:1294–1300. 2002. View Article : Google Scholar : PubMed/NCBI
77	Kudo Y, Ogawa I, Kitajima S, Kitagawa M, Kawai H, Gaffney PM, Miyauchi M and Takata T: Periotin promotes invasion and anchorage-independent growth in the metastatic process of head and neck cancer. Cancer Res. 66:6928–6935. 2006. View Article : Google Scholar : PubMed/NCBI
78	Malanchi I, Santamaria-Martínez A, Susanto E, Peng H, Lehr HA, Delaloye JF and Huelsken J: Interactions between cancer stem cells and their niche govern metastatic colonization. Nature. 481:85–89. 2011. View Article : Google Scholar : PubMed/NCBI
79	Kanno A, Satoh K, Masamune A, Hirota M, Kimura K, Umino J, Hamada S, Satoh A, Egawa S, Motoi F, Unno M and Shimosegawa T: Periostin, secreted from stromal cells, has biphasic effect on cell migration and correlates with the epitelial to mesenchymal transition of human pancreatic cancer cells. Int J Cancer. 22:2707–2718. 2008. View Article : Google Scholar : PubMed/NCBI
80	Kyutoku M, Taniyama Y, Katsuragi N, Shimizu H, Kunugiza Y, Iekushi K, Koibuchi N, Sanada F, Oshita Y and Morishita R: Role of periostin in cancer progression and metastasis: Inhibition of breast progression and metastasis by anti-periostin antibody in a murine model. Int J Mol Med. 28:181–186. 2011.PubMed/NCBI
81	Carter H, Samayoa J, Hruban RH and Karchin R: Prioritization of driver mutations in pancreatic cancer using cancer-specific high-throughput annotation of somatic mutations (CHASM). Cancer Biol Ther. 10:582–587. 2010. View Article : Google Scholar : PubMed/NCBI
82	Li Q and Wang L, Tan W, Peng Z, Luo Y, Zhang Y, Zhang G, Na D, Jin P, Shi T, Ma D and Wang L: Identification of C1qTNF-related protein 4 as a potential cytokine that stimulates the STAT3 and NF-κB pathways and promotes cell survival in human cancer cells. Cancer Lett. 28:203–214. 2011.PubMed/NCBI
83	Belirgen M, Berrak SG, Ozdag H, Bozkurt SU, Eksioglu-Demiralp E and Ozek MM: Biologic tumor behavior in pilocytic astrocytomas. Childs Nerv Syst. 28:375–389. 2012. View Article : Google Scholar : PubMed/NCBI
84	Huang YW, Jansen RA, Fabbri E, Potter D, Liyanarachchi S, Chan MW, Liu JC, Crijns AP, Brown R, Nephew KP, van der Zee AG, Cohn DE, Yan PS, Huang TH and Lin HJ: Identification of candidate epigenetic biomarkers for ovarian cancer detection. Oncol Rep. 22:853–861. 2009.PubMed/NCBI
85	Heller G, Babinsky VN, Ziegler B, Weinzierl M, Noll C, Altenberger C, Müllauer L, Dekan G, Grin Y, Lang G, End-Pfützenreuter A, Steiner I, Zehetmayer S, Döme B, Arns BM, Fong KM, Wright CM, Yang IA, Klepetko W, Posch M, Zielinski CC and Zöchbauer-Müller S: Genome-wide CpG island methylation analyses in non-small cell lung cancer patients. Carcinogenesis. 34:513–521. 2013. View Article : Google Scholar : PubMed/NCBI
86	Wirth T, Soeth E, Czubayko F and Juhl H: Inhibition of endogenous carcinoembryonic antigen (CEA) increases the apoptotic rate of colon cancer cells and inhibits metastatic tumor growth. Clin Exp Metastasis. 19:155–160. 2002. View Article : Google Scholar : PubMed/NCBI
87	Arrieta O, Saavedra-Perez D, Kuri R, Aviles-Salas A, Martinez L, Mendoza-Posada D, Castillo P, Astorga A, Guzman E and de la Garza J: Brain metastasis development and poor survival associated with carcinoembryonic antigen (CEA) level in advanced non-small cell lung cancer: a prospective analysis. BMC Cancer. 9:119–128. 2009. View Article : Google Scholar : PubMed/NCBI
88	Liebhardt S, Ditsch N, Nieuwland R, Rank A, Jeschke U, Von Koch F, Friese K and Toth B: CEA-, Her2/neu-, BCRP- and Hsp27-positive microparticles in breast cancer patients. Anticancer Res. 30:1707–1712. 2010.PubMed/NCBI