Hopx is methylated and exerts tumour-suppressive function through ras-induced senescence in human lung cancer

Journal of Pathology

Volumn 235, Issue 3, 2015, Pages 397-407

  Chen, Yuan ^a   Yang, Linlin ^a   Cui, Tiantian ^a   Pacyna Gengelbach, Manuela ^b   Petersen, Iver ^a  

^a JENA UNIVERSITY HOSPITAL   (Germany)

^b CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

Author keywords

HOPX; Lung cancer; Methylation; Ras induced senescence

Indexed keywords

HOMEODOMAIN PROTEIN; HOPX PROTEIN; MESSENGER RNA; MITOGEN ACTIVATED PROTEIN KINASE; PROTEIN MDM2; PROTEIN P21; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; HOP PROTEIN, HUMAN; RAS PROTEIN; TUMOR SUPPRESSOR PROTEIN;

ARTICLE; CANCER INHIBITION; CANCER PATIENT; CANCER SURVIVAL; CELL AGING; CONTROLLED STUDY; DISEASE FREE SURVIVAL; DNA METHYLATION; DOWN REGULATION; ENZYME INACTIVATION; EXPRESSION VECTOR; HUMAN; HUMAN CELL; HUMAN TISSUE; LUNG ADENOCARCINOMA; LUNG CANCER; LUNG CANCER CELL LINE; MIGRATION INHIBITION; ONCOGENE RAS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN METHYLATION; SQUAMOUS CELL LUNG CARCINOMA; STABLE TRANSFECTION; ADENOCARCINOMA; CELL CULTURE; CELL MOTION; CELL PROLIFERATION; COMPARATIVE STUDY; GENE EXPRESSION REGULATION; GENETICS; LUNG TUMOR; NON SMALL CELL LUNG CANCER; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; SIGNAL TRANSDUCTION; SMALL CELL LUNG CANCER; SQUAMOUS CELL CARCINOMA; TUMOR CELL LINE;

ADENOCARCINOMA; CARCINOMA, NON-SMALL-CELL LUNG; CARCINOMA, SQUAMOUS CELL; CELL AGING; CELL LINE, TUMOR; CELL MOVEMENT; CELL PROLIFERATION; CELLS, CULTURED; DNA METHYLATION; DOWN-REGULATION; GENE EXPRESSION REGULATION, NEOPLASTIC; HOMEODOMAIN PROTEINS; HUMANS; LUNG NEOPLASMS; RAS PROTEINS; SIGNAL TRANSDUCTION; SMALL CELL LUNG CARCINOMA; TUMOR SUPPRESSOR PROTEINS;

EID: 84920723622     PISSN: 00223417     EISSN: 10969896     Source Type: Journal    
DOI: 10.1002/path.4469     Document Type: Article

References (35)

1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012; 62: 10-29.
2. Spiro SG, Silvestri GA. One hundred years of lung cancer. Am J Respir Crit Care Med 2005; 172: 523-529.
3. Chen Y, Petersen S, Pacyna-Gengelbach M, et al. Identification of a novel homeobox-containing gene, LAGY, which is downregulated in lung cancer. Oncology 2003; 64: 450-458.
4. Chen Y, Pacyna-Gengelbach M, Deutschmann N, et al. Homeobox gene HOP has a potential tumor suppressive activity in human lung cancer. Int J Cancer 2007; 121: 1021-1027.
5. Waraya M, Yamashita K, Katoh H, et al. Cancer specific promoter CpG islands hypermethylation of HOP homeobox (HOPX) gene and its potential tumor suppressive role in pancreatic carcinogenesis. BMC Cancer 2012; 12: 397.
6. Harada Y, Kijima K, Shinmura K, et al. Methylation of the homeobox gene, HOPX, is frequently detected in poorly differentiated colorectal cancer. Anticancer Res 2011; 31: 2889-2892.
7. Ooki A, Yamashita K, Kikuchi S, et al. Potential utility of HOP homeobox gene promoter methylation as a marker of tumor aggressiveness in gastric cancer. Oncogene 2010; 29: 3263-3275.
8. Yamaguchi S, Asanoma K, Takao T, et al. Homeobox gene HOPX is epigenetically silenced in human uterine endometrial cancer and suppresses estrogen-stimulated proliferation of cancer cells by inhibiting serum response factor. Int J Cancer 2009; 124: 2577-2588.
9. Yamashita K, Kim MS, Park HL, et al. HOP/OB1/NECC1 promoter DNA is frequently hypermethylated and involved in tumorigenic ability in esophageal squamous cell carcinoma. Mol Cancer Res 2008; 6: 31-41.
10. Asanoma K, Matsuda T, Kondo H, et al. NECC1, a candidate choriocarcinoma suppressor gene that encodes a homeodomain consensus motif. Genomics 2003; 81: 15-25.
11. Chen F, Kook H, Milewski R, et al. Hop is an unusual homeobox gene that modulates cardiac development. Cell 2002; 110: 713-723.
12. Shin CH, Liu ZP, Passier R, et al. Modulation of cardiac growth and development by HOP, an unusual homeodomain protein. Cell 2002; 110: 725-735.
13. Yin Z, Gonzales L, Kolla V, et al. Hop functions downstream of Nkx2.1 and GATA6 tomediate HDAC-dependent negative regulation of pulmonary gene expression. Am J Physiol Lung Cell Mol Physiol 2006; 291: L191-L199.
14. Kee HJ, Kim JR, Nam KI, et al. Enhancer of polycomb1, a novel homeodomain only protein-binding partner, induces skeletal muscle differentiation. J Biol Chem 2007; 282: 7700-7709.
15. Asanoma K, Kato H, Inoue T, et al. Analysis of a candidate gene associated with growth suppression of choriocarcinoma and differentiation of trophoblasts. J Reprod Med 2004; 49: 617-626.
16. Vasiliev O, Rhodes SJ, Beebe DC. Identification and expression of Hop, an atypical homeobox gene expressed late in lens fiber cell terminal differentiation. Mol Vis 2007; 13: 114-124.
17. Takeda N, Jain R, LeBoeuf MR, et al. Interconversion between intestinal stem cell populations in distinct niches. Science 2011; 334: 1420-1424.
18. Takeda N, Jain R, Leboeuf MR, et al. Hopx expression defines a subset of multipotent hair follicle stem cells and a progenitor population primed to give rise to K6+ niche cells. Development 2013; 140: 1655-1664.
19. An Q, Pacyna-Gengelbach M, Schlüns K, et al. Identification of differentially expressed genes in immortalized human bronchial epithelial cell line as a model for in vitro study of lung carcinogenesis. Int J Cancer 2003; 103: 194-204.
20. Cui T, Chen Y, Yang L, et al. DSC3 expression is regulated by p53, and methylation of DSC3 DNA is a prognostic marker in human colorectal cancer. Br J Cancer 2011; 104: 1013-1019.
21. Chen Y, Pacyna-Gengelbach M, Ye F, et al. Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) has potential tumour-suppressive activity in human lung cancer. J Pathol 2007; 211: 431-438.
22. Yang L, Chen Y, Cui T, et al. Desmoplakin acts as a tumor suppressor by inhibition of the Wnt/beta-catenin signaling pathway in human lung cancer. Carcinogenesis 2012; 33: 1863-1870.
23. Lowe SW, Cepero E, Evan G. Intrinsic tumour suppression. Nature 2004; 432: 307-315.
24. Serrano M, Lin AW, McCurrach ME, et al. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a . Cell 1997; 88: 593-602.
25. Wang W, Chen JX, Liao R, et al. Sequential activation of the MEKextracellular signal-regulated kinase and MKK3/6-p38 mitogenactivated protein kinase pathways mediates oncogenic ras-induced premature senescence. Mol Cell Biol 2002; 22: 3389-3403.
26. Deng Q, Li Y, Tedesco D, Liao R, et al. The ability of E1A to rescue ras-induced premature senescence and confer transformation relies on inactivation of both p300/CBP and Rb family proteins. Cancer Res 2005; 65: 8298-8307.
27. Cheung WK, Zhao M, Liu Z, et al. Control of alveolar differentiation by the lineage transcription factors GATA6 and HOPX inhibits lung adenocarcinoma metastasis. Cancer Cell 2013; 23: 725-738.
28. Kovárová D, Plachy J, Kosla J, et al. Downregulation of HOPX controls metastatic behavior in sarcoma cells and identifies genes associated with metastasis. Mol Cancer Res 2013, 11: 1235-1247.
29. Pearson M, Carbone R, Sebastiani C, et al. PML regulates p53 acetylation and premature senescence induced by oncogenic Ras. Nature 2000; 406: 207-210.
30. Zhu J,Woods D, McMahon M, et al. Senescence of human fibroblasts induced by oncogenic Raf. Genes Dev 1998; 12: 2997-3007.
31. Ben-Porath I, Weinberg RA. The signals and pathways activating cellular senescence. Int J Biochem Cell Biol 2005; 37: 961-976.
32. Hanahan D,Weinberg RA. The hallmarks of cancer. Cell 2000; 100: 57-70.
33. Kennedy AL, Adams PD, Morton JP. Ras, PI3K/Akt and senescence: paradoxes provide clues for pancreatic cancer therapy. Small GTPases 2011; 2: 264-267.
34. Astle MV, Hannan KM, Ng PY, et al. AKT induces senescence in human cells via mTORC1 and p53 in the absence of DNA damage: implications for targeting mTOR during malignancy. Oncogene 2012; 31: 1949-1962.
35. Westbrook TF, Nguyen DX, Thrash BR, et al. E7 abolishes Raf-induced arrest via mislocalization of p21Cip1 . Mol Cell Biol 2002; 22: 7041-7052.