nach oben

Journal of Cancer Research and Clinical Oncology

Erschienen in:

01.09.2015 | Original Article – Cancer Research

Cullin1 is a novel prognostic marker and regulates the cell proliferation and metastasis in colorectal cancer

verfasst von: Weimin Wang, Yansu Chen, Jianliang Deng, Jianping Zhou, Xiancheng Gu, Yuehua Tang, Guoqiang Zhang, Yongfei Tan, Zhijun Ge, Yulin Huang, Shouyu Wang, Jianwei Zhou, Yan Zhou, Sujun Zhou

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 9/2015

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To investigate the precise function of Cullin1 (CUL1) in colorectal cancer (CRC).

Methods

Immunohistochemistry was performed to test the expression of CUL1 on a CRC tissue microarray containing the tumor and corresponding normal tissues. Simultaneously, the correlation of CUL1 expression with clinicopathological parameters and survival was evaluated. CUL1 was over-expressed or knocked down in HCT116 and SW480 cells, then the cell proliferation, migration and invasion assays in vitro and in vivo were performed.

Results

In this study, we found that CUL1 expression was significantly up-regulated in CRC compared with normal colon tissues. High CUL1 expression was positively associated with lymph node metastasis (P = 0.007) and tumor diameter (P = 0.052). Multivariate Cox regression analysis revealed that high CUL1 expression was an independent unfavorable prognostic factor for CRC patients (HR = 13.9, 95 % confidence interval = 5.89–32.6, P < 0.001). Moreover, we found that CUL1 over-expression induced CRC cell proliferation and the growth of xenografts in nude mice via the changing of cell-cycle proteins. In addition, increased CUL1 expression in CRC cells significantly promoted cell migration and invasion abilities in vitro and peritoneal metastasis in vivo through inducing high expression of MMPs.

Conclusion

Our findings imply that CUL1 may serve as promising prognostic markers in CRC patients.

Nur mit Berechtigung zugänglich

Bai J, Zhang J, Wu J, Shen L, Zeng J, Ding J, Wu Y, Gong Z, Li A, Xu S, Zhou J, Li G (2010) JWA regulates melanoma metastasis by integrin alphaVbeta3 signaling. Oncogene 29:1227–1237. doi:10.1038/onc.2009.408 CrossRefPubMed

Bai J, Zhou Y, Chen G, Zeng J, Ding J, Tan Y, Zhou J, Li G (2011) Overexpression of Cullin1 is associated with poor prognosis of patients with gastric cancer. Hum Pathol 42:375–383. doi:10.1016/j.humpath.2010.09.003 CrossRefPubMed

Bai J, Yong HM, Chen FF, Mei PJ, Liu H, Li C, Pan ZQ, Wu YP, Zheng JN (2013) Cullin1 is a novel marker of poor prognosis and a potential therapeutic target in human breast cancer. Ann Oncol 24:2016–2022. doi:10.1093/annonc/mdt147 CrossRefPubMed

Chaudhary AK, Pandya S, Ghosh K, Nadkarni A (2013) Matrix metalloproteinase and its drug targets therapy in solid and hematological malignancies: an overview. Mutat Res 753:7–23. doi:10.1016/j.mrrev.2013.01.002 CrossRefPubMed

Chen G, Li G (2010) Increased Cul1 expression promotes melanoma cell proliferation through regulating p27 expression. Int J Oncol 37:1339–1344PubMed

Chen G, Cheng Y, Martinka M, Li G (2010) Cul1 expression is increased in early stages of human melanoma. Pigment Cell Melanoma Res 23:572–574. doi:10.1111/j.1755-148X.2010.00725.x CrossRefPubMed

Denicourt C, Dowdy SF (2004) Cip/Kip proteins: more than just CDKs inhibitors. Genes Dev 18:851–855. doi:10.1101/gad.1205304 CrossRefPubMed

Guardavaccaro D, Pagano M (2006) Stabilizers and destabilizers controlling cell cycle oscillators. Mol Cell 22:1–4. doi:10.1016/j.molcel.2006.03.017 CrossRefPubMed

Gupta GP, Massague J (2006) Cancer metastasis: building a framework. Cell 127:679–695. doi:10.1016/j.cell.2006.11.001 CrossRefPubMed

Hynes RO (2003) Metastatic potential: generic predisposition of the primary tumor or rare, metastatic variants-or both? Cell 113:821–823CrossRefPubMed

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90. doi:10.3322/caac.20107 CrossRefPubMed

Libra M, Scalisi A, Vella N, Clementi S, Sorio R, Stivala F, Spandidos DA, Mazzarino C (2009) Uterine cervical carcinoma: role of matrix metalloproteinases (review). Int J Oncol 34:897–903PubMed

Mocciaro A, Rape M (2012) Emerging regulatory mechanisms in ubiquitin-dependent cell cycle control. J Cell Sci 125:255–263. doi:10.1242/jcs.091199 PubMedCentralCrossRefPubMed

Nakayama KI, Nakayama K (2006) Ubiquitin ligases: cell-cycle control and cancer. Nat Rev Cancer 6:369–381. doi:10.1038/nrc1881 CrossRefPubMed

Nguyen DX, Massague J (2007) Genetic determinants of cancer metastasis. Nat Rev Genet 8:341–352. doi:10.1038/nrg2101 CrossRefPubMed

Salon C, Brambilla E, Brambilla C, Lantuejoul S, Gazzeri S, Eymin B (2007) Altered pattern of Cul-1 protein expression and neddylation in human lung tumours: relationships with CAND1 and cyclin E protein levels. J Pathol 213:303–310. doi:10.1002/path.2223 CrossRefPubMed

Schmoll HJ, Stein A (2014) Colorectal cancer in 2013: towards improved drugs, combinations and patient selection. Nat Rev Clin Oncol. doi:10.1038/nrclinonc.2013.254 PubMed

Sun Y, Shen S, Liu X, Tang H, Wang Z, Yu Z, Li X, Wu M (2014) miR-429 inhibits cells growth and invasion and regulates EMT-related marker genes by targeting Onecut2 in colorectal carcinoma. Mol Cell Biochem. doi:10.1007/s11010-013-1950-x PubMedCentral

von Wasielewski R, Mengel M, Wiese B, Rudiger T, Muller-Hermelink HK, Kreipe H (2002) Tissue array technology for testing interlaboratory and interobserver reproducibility of immunohistochemical estrogen receptor analysis in a large multicenter trial. Am J Clin Pathol 118:675–682. doi:10.1309/URLK-6AVK-331U-0V5P CrossRef

Wang S, Wu X, Zhang J, Chen Y, Xu J, Xia X, He S, Qiang F, Li A, Shu Y, Roe OD, Li G, Zhou JW (2013) CHIP functions as a novel suppressor of tumour angiogenesis with prognostic significance in human gastric cancer. Gut 62:496–508. doi:10.1136/gutjnl-2011-301522 CrossRefPubMed

Xie CM, Wei W, Sun Y (2013) Role of SKP1-CUL1-F-box-protein (SCF) E3 ubiquitin ligases in skin cancer. J Genet Genomics 40:97–106. doi:10.1016/j.jgg.2013.02.001 CrossRefPubMed

Zheng N, Schulman BA, Song L, Miller JJ, Jeffrey PD, Wang P, Chu C, Koepp DM, Elledge SJ, Pagano M, Conaway RC, Conaway JW, Harper JW, Pavletich NP (2002) Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex. Nature 416:703–709. doi:10.1038/416703a CrossRefPubMed

Titel: Cullin1 is a novel prognostic marker and regulates the cell proliferation and metastasis in colorectal cancer
verfasst von: Weimin Wang
Yansu Chen
Jianliang Deng
Jianping Zhou
Xiancheng Gu
Yuehua Tang
Guoqiang Zhang
Yongfei Tan
Zhijun Ge
Yulin Huang
Shouyu Wang
Jianwei Zhou
Yan Zhou
Sujun Zhou
Publikationsdatum: 01.09.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 9/2015
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-015-1931-4

Springer Medizin

Cullin1 is a novel prognostic marker and regulates the cell proliferation and metastasis in colorectal cancer