title: Abrogation of galectin-4 expression promotes tumorigenesis in colorectal cancer.
abstract: BACKGROUND
  Although it has been well established that galectin-4 is selectively expressed by intestinal epithelial cells, the role of galectin-4 in colorectal cancer (CRC) development is, as yet, poorly understood. Here, we aimed to explore the role of galectin-4 in CRC development, both in vitro and in vivo.
  
  
  METHODS
  Galectin-4 expression was investigated in tissue specimens from patients with adenoma, carcinoma and ulcerative colitis (UC) using immunohistochemistry. Colorectal cancer-derived HT-29 cells, in which galectin-4 expression was knocked down, were established using shRNA. mRNA and protein expression levels of galectin-4 and several downstream cancer-related genes were analyzed using RT-PCR, qPCR array, Western blotting, and immunofluorescence assays. To investigate the effect of galectin-4 expression abrogation on tumorigenesis in vivo, xenograft assays were performed.
  
  
  RESULTS
  Immunohistochemistry analyses showed high expression levels of galectin-4 in normal colon mucosa tissues. Conversely, the expression levels of galectin-4 were significantly lower in CRC samples and its precursor lesions with dysplasia or inflammation. We found that shRNA-mediated galectin-4 silencing increases cell proliferation and, concomitantly, activates NF-κB and STAT3 signaling along with IL-6 up-regulation. In addition, we found that shRNA-mediated galectin-4 silencing promotes the expression of NF-κB target genes and other cancer-related genes and, concomitantly, enhances the in vivo growth of xenografts.
  
  
  CONCLUSIONS
  We show that abrogation of galectin-4 expression promotes cancer cell proliferation and, for the first time, provide evidence that down-regulation of galectin-4 elicits tumor promotion in vitro and in vivo through activation of IL-6/NF-κB/STAT3 signaling.
authors: Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.
authors: Seung Won
authors: SW
authors: Kim
authors: Ki Cheong
authors: KC
authors: Park
authors: Soung Min
authors: SM
authors: Jeon
authors: Tak Bum
authors: TB
authors: Ohn
authors: Tae Il
authors: TI
authors: Kim
authors: Won Ho
authors: WH
authors: Kim
authors: Jae Hee
authors: JH
authors: Cheon
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D037541:Galectin 4 / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D014183:Transplantation, Heterologous; D047368:Tumor Burden
chemical_list: D037541:Galectin 4; D015850:Interleukin-6; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
references: Hum Pathol. 2011 May;42(5):688-701
references: 21237495
references: J Immunother. 1999 Jan;22(1):25-32
references: 9924696
references: Annu Rev Biochem. 2000;69:145-82
references: 10966456
references: Carcinogenesis. 2000 May;21(5):973-6
references: 10783320
references: FASEB J. 2001 Dec;15(14):2742-4
references: 11606477
references: J Surg Oncol. 2003 Aug;83(4):222-6
references: 12884234
references: Int J Colorectal Dis. 2008 Jun;23(6):569-80
references: 18305945
references: Mol Cell. 2007 Sep 21;27(6):992-1004
references: 17889671
references: Cytokine Growth Factor Rev. 2010 Feb;21(1):11-9
references: 20018552
references: Cancer Res. 2010 Feb 15;70(4):1469-78
references: 20145124
references: J Histochem Cytochem. 2005 Feb;53(2):197-205
references: 15684332
references: Annu Rev Pharmacol Toxicol. 1998;38:97-120
references: 9597150
references: Tissue Antigens. 2004 Jul;64(1):1-12
references: 15191517
references: Nat Cell Biol. 2007 Dec;9(12):1419-27
references: 18037881
references: Gut. 2010 Feb;59(2):227-35
references: 19926618
references: Breast Cancer Res. 2006;8(4):R37
references: 16846534
references: Oncogene. 2012 Jul 19;31(29):3467-81
references: 22105366
references: Nat Rev Immunol. 2009 May;9(5):338-52
references: 19365409
references: Cell. 2009 Nov 13;139(4):693-706
references: 19878981
references: Hum Immunol. 2009 Mar;70(3):151-8
references: 19272324
references: Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2207-11
references: 8384717
references: Glycoconj J. 2004;20(4):247-55
references: 15115909
references: Histopathology. 2002 May;40(5):440-9
references: 12010364
references: Clin Cancer Res. 2011 Nov 15;17(22):7035-46
references: 21933892
references: PLoS One. 2008 Jul 09;3(7):e2629
references: 18612433
references: Cancer Cell. 2008 Jan;13(1):7-9
references: 18167335
references: Cell. 2002 Oct 18;111(2):241-50
references: 12408868
references: Biochem J. 2000 Aug 1;349 Pt 3:765-73
references: 10903137
references: Prostate. 2001 Jun 15;48(1):47-53
references: 11391686
references: Cancer Res. 2001 Jun 1;61(11):4628-35
references: 11389100
references: Carcinogenesis. 2001 Jun;22(6):869-74
references: 11375891
references: Inflamm Bowel Dis. 2010 Sep;16(9):1514-25
references: 20310012
references: Biochem Biophys Res Commun. 2007 Mar 2;354(1):165-71
references: 17214970
references: Clin Cancer Res. 2007 Nov 1;13(21):6459-68
references: 17975158
references: J Immunol. 1992 May 15;148(10):3152-7
references: 1315830
references: Cancer Res. 2000 Mar 1;60(5):1306-11
references: 10728691
references: Cancer Cell. 2009 Feb 3;15(2):103-13
references: 19185845
references: Oncogene. 2003 Mar 13;22(10):1517-27
references: 12629515
references: EMBO Rep. 2009 Dec;10(12):1314-9
references: 19893576
references: Oncol Rep. 2011 May;25(5):1217-26
references: 21369702
references: J Biol Chem. 2004 Jan 16;279(3):1768-76
references: 14593105
references: Clin Immunol. 2000 Nov;97(2):79-88
references: 11027447
references: Int J Cancer. 2011 Aug 15;129(4):799-809
references: 21064109
references: Cancer Cell. 2009 Apr 7;15(4):283-93
references: 19345327
references: Neoplasia. 2005 Jun;7(6):545-55
references: 16036105
references: Virchows Arch. 2002 Jun;440(6):594-7
references: 12070598
references: Biochem Pharmacol. 2000 Oct 15;60(8):1185-95
references: 11007957
references: Br J Cancer. 2010 Sep 7;103(6):787-95
references: 20823887
references: Anal Quant Cytol Histol. 2001 Aug;23(4):291-9
references: 11531144
references: Immunity. 2004 Jun;20(6):681-93
references: 15189734
references: J Cell Biochem. 2002;86(4):759-72
references: 12210742
references: J Immunol. 2011 Mar 15;186(6):3283-8
references: 21368237
references: J Biol Chem. 2002 Mar 29;277(13):11116-25
references: 11799112