nach oben

Erschienen in:

01.02.2015 | Research Paper

HES1 promotes metastasis and predicts poor survival in patients with colorectal cancer

verfasst von: Ruixue Yuan, Jia Ke, Lei Sun, Zhen He, Yifeng Zou, Xiaosheng He, Yufeng Chen, Xianrui Wu, Zerong Cai, Lei Wang, Jianping Wang, Xinjuan Fan, Xiaojian Wu, Ping Lan

Erschienen in: Clinical & Experimental Metastasis | Ausgabe 2/2015

Einloggen, um Zugang zu erhalten

Abstract

Hairy enhancer of split-1 (HES1) is a transcriptional target of the Notch pathway, and a high level of HES1 is regarded as a marker of activated Notch. The aim of the study was to investigate the role of HES1 in colorectal cancer progression. We used tissue microarrays to analyze the expression and clinical significance of HES1 in 320 colorectal cancer samples. Stable overexpression and knockdown of HES1 were established in three colorectal cancer cell (CRC) lines (RKO, HCT8 and LOVO). We investigated the differentially expressed genes and enriched pathways in HES1 overexpressing CRC cells by gene expression profiling. Also, the role of HES1 in invasion and migration were examined in vitro and in vivo. We found that high expression of HES1 was significantly correlated with distal metastasis (P = 0.037) at diagnosis, and HES1 could serve as an unfavorable prognostic factor for colorectal cancer patients (P = 0.034). Gene expression profiling and pathway enrichment analysis revealed that HES1 was related to cellular adherens junction loss. In addition, we showed that HES1 overexpression lead to depressed E-cadherin, and elevated N-cadherin, vimentin and Twist-1 levels. Functionally, HES1 enhanced invasiveness and metastasis of CRC cells. HES1 promotes cancer metastasis via inducing epithelial mesenchymal transition and serves as a poor prognosis factor of colorectal cancer patients.

Jemal A, Bray F, Center MM et al (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90. doi:10.3322/caac.20107 PubMedCrossRef

Bengtsson G, Carlsson G, Hafstrom L et al (1981) Natural history of patients with untreated liver metastases from colorectal cancer. Am J Surg 141(5):586–589PubMedCrossRef

Brenner H, Bouvier AM, Foschi R et al (2012) Progress in colorectal cancer survival in Europe from the late 1980s to the early 21st century: the EUROCARE study. Int J Cancer 131(7):1649–1658. doi:10.1002/ijc.26192 PubMedCrossRef

Artavanis-Tsakonas S, Rand MD, Lake RJ (1999) Notch signaling: cell fate control and signal integration in development. Science 284(5415):770–776PubMedCrossRef

Wang Z, Li Y, Banerjee S et al (2009) Emerging role of Notch in stem cells and cancer. Cancer Lett 279(1):8–12. doi:10.1016/j.canlet.2008.09.030 PubMedCentralPubMedCrossRef

Radtke F, Raj K (2003) The role of Notch in tumorigenesis: oncogene or tumour suppressor? Nat Rev Cancer 3(10):756–767. doi:10.1038/nrc1186 PubMedCrossRef

Kageyama R, Ohtsuka T, Kobayashi T (2007) The Hes gene family: repressors and oscillators that orchestrate embryogenesis. Development 134(7):1243–1251. doi:10.1242/dev.000786 PubMedCrossRef

Sang L, Roberts JM, Coller HA (2010) Hijacking HES1: how tumors co-opt the anti-differentiation strategies of quiescent cells. Trends Mol Med 16(1):17–26. doi:10.1016/j.molmed.2009.11.001 PubMedCentralPubMedCrossRef

Ramskold D, Luo S, Wang YC et al (2012) Full-length mRNA-seq from single-cell levels of RNA and individual circulating tumor cells. Nat Biotechnol 30(8):777–782. doi:10.1038/nbt.2282 PubMedCentralPubMedCrossRef

10.

Zhang P, Yang Y, Zweidler-McKay PA et al (2008) Critical role of notch signaling in osteosarcoma invasion and metastasis. Clin Cancer Res 14(10):2962–2969. doi:10.1158/1078-0432.CCR-07-1992 PubMedCentralPubMedCrossRef

11.

Zhang P, Yang Y, Nolo R et al (2010) Regulation of NOTCH signaling by reciprocal inhibition of HES1 and Deltex 1 and its role in osteosarcoma invasiveness. Oncogene 29(20):2916–2926. doi:10.1038/onc.2010.62 PubMedCentralPubMedCrossRef

12.

Fan X, Mikolaenko I, Elhassan I et al (2004) Notch1 and notch2 have opposite effects on embryonal brain tumor growth. Cancer Res 64(21):7787–7793. doi:10.1158/0008-5472.CAN-04-1446 PubMedCrossRef

13.

Wang X, Fu Y, Chen X et al (2010) The expressions of bHLH gene HES1 and HES5 in advanced ovarian serous adenocarcinomas and their prognostic significance: a retrospective clinical study. J Cancer Res Clin Oncol 136(7):989–996. doi:10.1007/s00432-009-0744-8 PubMedCentralPubMedCrossRef

14.

Kinzler KW, Nilbert MC, Su LK et al (1991) Identification of FAP locus genes from chromosome 5q21. Science 253(5020):661–665PubMedCrossRef

15.

Reedijk M, Odorcic S, Zhang H et al (2008) Activation of Notch signaling in human colon adenocarcinoma. Int J Oncol 33(6):1223–1229PubMedCentralPubMed

16.

Veenendaal LM, Kranenburg O, Smakman N et al (2008) Differential Notch and TGFbeta signaling in primary colorectal tumors and their corresponding metastases. Cell Oncol 30(1):1–11PubMed

17.

Meng RD, Shelton CC, Li YM et al (2009) gamma-Secretase inhibitors abrogate oxaliplatin-induced activation of the Notch-1 signaling pathway in colon cancer cells resulting in enhanced chemosensitivity. Cancer Res 69(2):573–582. doi:10.1158/0008-5472.CAN-08-2088 PubMedCentralPubMedCrossRef

18.

Gao F, Zhang Y, Wang S et al (2014) Hes1 is involved in the self-renewal and tumourigenicity of stem-like cancer cells in colon cancer. Sci Rep 4:3963. doi:10.1038/srep03963 PubMedCentralPubMed

19.

Ingram WJ, McCue KI, Tran TH et al (2008) Sonic Hedgehog regulates Hes1 through a novel mechanism that is independent of canonical Notch pathway signalling. Oncogene 27(10):1489–1500. doi:10.1038/sj.onc.1210767 PubMedCrossRef

20.

Stockhausen MT, Sjolund J, Axelson H (2005) Regulation of the Notch target gene Hes-1 by TGFalpha induced Ras/MAPK signaling in human neuroblastoma cells. Exp Cell Res 310(1):218–228. doi:10.1016/j.yexcr.2005.07.011 PubMedCrossRef

21.

Curry CL, Reed LL, Golde TE et al (2005) Gamma secretase inhibitor blocks Notch activation and induces apoptosis in Kaposi’s sarcoma tumor cells. Oncogene 24(42):6333–6344. doi:10.1038/sj.onc.1208783 PubMed

22.

Wu XR, He XS, Chen YF et al (2012) High expression of CD73 as a poor prognostic biomarker in human colorectal cancer. J Surg Oncol 106(2):130–137. doi:10.1002/jso.23056 PubMedCrossRef

23.

Rhodes DR, Yu J, Shanker K et al (2004) ONCOMINE: a cancer microarray database and integrated data-mining platform. Neoplasia 6(1):1–6PubMedCentralPubMedCrossRef

24.

Yu X, Alder JK, Chun JH et al (2006) HES1 inhibits cycling of hematopoietic progenitor cells via DNA binding. Stem Cells 24(4):876–888. doi:10.1634/stemcells.2005-0598 PubMedCrossRef

25.

Adams JC (2004) Roles of fascin in cell adhesion and motility. Curr Opin Cell Biol 16(5):590–596. doi:10.1016/j.ceb.2004.07.009 PubMedCrossRef

26.

Lokeshwar VB, Cerwinka WH, Isoyama T et al (2005) HYAL1 hyaluronidase in prostate cancer: a tumor promoter and suppressor. Cancer Res 65(17):7782–7789. doi:10.1158/0008-5472.CAN-05-1022 PubMed

27.

Turner CE (2000) Paxillin and focal adhesion signalling. Nat Cell Biol 2(12):E231–E236. doi:10.1038/35046659 PubMedCrossRef

28.

Qiao L, Wong BC (2009) Role of Notch signaling in colorectal cancer. Carcinogenesis 30(12):1979–1986. doi:10.1093/carcin/bgp236 PubMedCrossRef

29.

Candy PA, Phillips MR, Redfern AD et al (2013) Notch-induced transcription factors are predictive of survival and 5-fluorouracil response in colorectal cancer patients. Br J Cancer 109(4):1023–1030. doi:10.1038/bjc.2013.431 PubMedCentralPubMedCrossRef

30.

Rhodes DR, Kalyana-Sundaram S, Mahavisno V et al (2007) Oncomine 3.0: genes, pathways, and networks in a collection of 18,000 cancer gene expression profiles. Neoplasia 9(2):166–180PubMedCentralPubMedCrossRef

31.

Wang Z, Banerjee S, Li Y et al (2006) Down-regulation of notch-1 inhibits invasion by inactivation of nuclear factor-kappaB, vascular endothelial growth factor, and matrix metalloproteinase-9 in pancreatic cancer cells. Cancer Res 66(5):2778–2784. doi:10.1158/0008-5472.CAN-05-4281 PubMedCrossRef

32.

Balint K, Xiao M, Pinnix CC et al (2005) Activation of Notch1 signaling is required for beta-catenin-mediated human primary melanoma progression. J Clin Invest 115(11):3166–3176. doi:10.1172/JCI25001 PubMedCentralPubMedCrossRef

33.

Bennani-Baiti IM, Aryee DN, Ban J et al (2011) Notch signalling is off and is uncoupled from HES1 expression in Ewing’s sarcoma. J Pathol 225(3):353–363. doi:10.1002/path.2966 PubMedCrossRef

34.

Thiery JP, Sleeman JP (2006) Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol 7(2):131–142. doi:10.1038/nrm1835 PubMedCrossRef

35.

Sonoshita M, Aoki M, Fuwa H et al (2011) Suppression of colon cancer metastasis by Aes through inhibition of Notch signaling. Cancer Cell 19(1):125–137. doi:10.1016/j.ccr.2010.11.008 PubMedCrossRef

36.

Kang Y, Massague J (2004) Epithelial-mesenchymal transitions: twist in development and metastasis. Cell 118(3):277–279. doi:10.1016/j.cell.2004.07.011 PubMedCrossRef

37.

Grunert S, Jechlinger M, Beug H (2003) Diverse cellular and molecular mechanisms contribute to epithelial plasticity and metastasis. Nat Rev Mol Cell Biol 4(8):657–665. doi:10.1038/nrm1175 PubMedCrossRef

38.

Sahlgren C, Gustafsson MV, Jin S et al (2008) Notch signaling mediates hypoxia-induced tumor cell migration and invasion. Proc Natl Acad Sci USA 105(17):6392–6397. doi:10.1073/pnas.0802047105 PubMedCentralPubMedCrossRef

39.

Becker KF, Rosivatz E, Blechschmidt K et al (2007) Analysis of the E-cadherin repressor Snail in primary human cancers. Cells Tissues Organs 185(1–3):204–212. doi:10.1159/000101321 PubMedCrossRef

40.

Niessen K, Fu Y, Chang L et al (2008) Slug is a direct Notch target required for initiation of cardiac cushion cellularization. J Cell Biol 182(2):315–325. doi:10.1083/jcb.200710067 PubMedCentralPubMedCrossRef

41.

Mani SA, Guo W, Liao MJ et al (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133(4):704–715. doi:10.1016/j.cell.2008.03.027 PubMedCentralPubMedCrossRef

42.

Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674. doi:10.1016/j.cell.2011.02.013 PubMedCrossRef

43.

Moon CM, Kwon JH, Kim JS et al (2014) Nonsteroidal anti-inflammatory drugs suppress cancer stem cells via inhibiting PTGS2 (cyclooxygenase 2) and NOTCH/HES1 and activating PPARG in colorectal cancer. Int J Cancer 134(3):519–529. doi:10.1002/ijc.28381 PubMedCrossRef

Titel: HES1 promotes metastasis and predicts poor survival in patients with colorectal cancer
verfasst von: Ruixue Yuan
Jia Ke
Lei Sun
Zhen He
Yifeng Zou
Xiaosheng He
Yufeng Chen
Xianrui Wu
Zerong Cai
Lei Wang
Jianping Wang
Xinjuan Fan
Xiaojian Wu
Ping Lan
Publikationsdatum: 01.02.2015
Verlag: Springer Netherlands
Erschienen in: Clinical & Experimental Metastasis / Ausgabe 2/2015
Print ISSN: 0262-0898
Elektronische ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-015-9700-y

Springer Medizin

HES1 promotes metastasis and predicts poor survival in patients with colorectal cancer

Abstract

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2015

Bladder metastasis from renal cell carcinoma: retrospective analysis of 65 reported cases

Lenalidomide and cyclophosphamide immunoregulation in patients with metastatic, castration-resistant prostate cancer

HER2 and β-catenin protein location: importance in the prognosis of breast cancer patients and their correlation when breast cancer cells suffer stressful situations

Pattern of metastasis and outcome in patients with breast cancer

Epigenetic variations in breast cancer progression to lymph node metastasis

Prognostic significance of histology after resection of brain metastases and whole brain radiotherapy in non-small cell lung cancer (NSCLC)

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie