title: S100A8 and S100A9 are associated with colorectal carcinoma progression and contribute to colorectal carcinoma cell survival and migration via Wnt/β-catenin pathway.
abstract: OBJECTIVE
  S100A8 and S100A9, two members of the S100 protein family, have been reported in association with the tumor cell differentiation and tumor progression. Previous study has showed that their expression in stromal cells of colorectal carcinoma (CRC) is associated with tumor size. Here, we investigated the clinical significances of S100A8 and S100A9 in tumor cells of CRC and their underlying molecular mechanisms.
  
  
  METHODS
  Expression of S100A8 and S100A9 in colorectal carcinoma and matching distal normal tissues were measured by reverse transcriptase polymerase chain reaction (RT-PCR), immunohistochemistry and western blot. CRC cell lines treated with the recombinant S100A8 and S100A9 proteins were used to analyze the roles and molecular mechanisms of the two proteins in CRC in vitro.
  
  
  RESULTS
  S100A8 and S100A9 were elevated in more than 50% of CRC tissues and their expression in tumor cells was associated with differentiation, Dukes stage and lymph node metastasis. The CRC cell lines treatment with recombinant S100A8 and S100A9 proteins promoted the viability and migration of CRC cells. Furthermore, the two recombinant proteins also resulted in the increased levels of β-catenin and its target genes c-myc and MMP7. β-catenin over-expression in CRC cells by Adβ-catenin increased cell viability and migration. β-catenin knock-down by Adsiβ-catenin reduced cell viability and migration. Furthermore, β-catenin knockdown also partially abolished the promotive effects of recombinant S100A8 and S100A9 proteins on the viability and migration of CRC cells.
  
  
  CONCLUSIONS
  Our work demonstrated that S100A8 and S100A9 are linked to the CRC progression, and one of the underlying molecular mechanisms is that extracellular S100A8 and S100A9 proteins contribute to colorectal carcinoma cell survival and migration via Wnt/β-catenin pathway.
authors: Key Laboratory of Diagnostic Medicine designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China.
authors: Liang
authors: L
authors: Duan
authors: Rui
authors: R
authors: Wu
authors: Liwei
authors: L
authors: Ye
authors: Haiyan
authors: H
authors: Wang
authors: Xia
authors: X
authors: Yang
authors: Yunyuan
authors: Y
authors: Zhang
authors: Xian
authors: X
authors: Chen
authors: Guowei
authors: G
authors: Zuo
authors: Yan
authors: Y
authors: Zhang
authors: Yaguang
authors: Y
authors: Weng
authors: Jinyong
authors: J
authors: Luo
authors: Min
authors: M
authors: Tang
authors: Qiong
authors: Q
authors: Shi
authors: Tongchuan
authors: T
authors: He
authors: Lan
authors: L
authors: Zhou
mesh_terms: D000368:Aged; D040501:Calgranulin A / Q000378:metabolism*; D040502:Calgranulin B / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D008875:Middle Aged; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism
chemical_list: D040501:Calgranulin A; D040502:Calgranulin B; D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins; D051176:beta Catenin; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7
references: PLoS One. 2012;7(2):e29333
references: 22363402
references: Science. 2008 May 2;320(5876):667-70
references: 18451303
references: Nat Rev Cancer. 2008 May;8(5):387-98
references: 18432252
references: Electrophoresis. 1999 Apr-May;20(4-5):1047-54
references: 10344284
references: Carcinogenesis. 2010 Sep;31(9):1541-51
references: 20622003
references: Carcinogenesis. 2008 Oct;29(10):2035-43
references: 18689872
references: Int J Biochem Cell Biol. 2001 Jul;33(7):637-68
references: 11390274
references: Biochem Biophys Res Commun. 2003 Jul 25;307(2):375-81
references: 12859967
references: Mediators Inflamm. 2005 Oct 24;2005(5):280-92
references: 16258195
references: Digestion. 2002;66(3):131-44
references: 12481159
references: J Cell Biochem. 2007 Nov 1;102(4):820-8
references: 17854061
references: Front Biosci. 2002 May 01;7:d1356-68
references: 11991838
references: Int J Oncol. 2013 Mar;42(3):1001-10
references: 23354417
references: Cancer Res. 2010 Jan 1;70(1):266-76
references: 20028853
references: J Biol Chem. 2011 Oct 7;286(40):35061-70
references: 21844192
references: Cell. 2000 Oct 13;103(2):311-20
references: 11057903
references: Cancer. 2010 Feb 1;116(3):544-73
references: 19998273
references: Clin Cancer Res. 2005 Jul 15;11(14):5146-52
references: 16033829
references: Cell. 1999 Jun 25;97(7):889-901
references: 10399917
references: Anticancer Res. 2009 Oct;29(10):4157-61
references: 19846966
references: World J Gastroenterol. 2008 Oct 21;14(39):6052-9
references: 18932285
references: Nat Med. 2010 Jun;16(6):713-7
references: 20473308
references: J Leukoc Biol. 2009 Sep;86(3):557-66
references: 19451397
references: Cell. 2002 Oct 18;111(2):241-50
references: 12408868
references: Gastroenterology. 2009 Jul;137(1):165-75
references: 19328798
references: Cancer Res. 2004 Dec 15;64(24):9018-26
references: 15604267
references: Science. 2007 May 18;316(5827):1043-6
references: 17510365
references: Exp Cell Res. 2006 Jan 15;312(2):184-97
references: 16297907
references: Chemotherapy. 2006;52(1):32-4
references: 16340196
references: Cell Res. 2010 Mar;20(3):314-31
references: 19935772
references: Histopathology. 2005 Mar;46(3):256-69
references: 15720411
references: Eur J Pharmacol. 2009 Dec 25;625(1-3):73-83
references: 19835859
references: Pathol Oncol Res. 2010 Sep;16(3):353-60
references: 19957061
references: Nat Cell Biol. 2010 May;12(5):468-76
references: 20418870
references: Cancer Res. 2002 Dec 1;62(23):6823-6
references: 12460893
references: Mol Cell Biol. 2003 Feb;23(3):1034-43
references: 12529407
references: Mol Cancer Res. 2011 Feb;9(2):133-48
references: 21228116
references: For Immunopathol Dis Therap. 2010;1(3):155-181
references: 21686046
references: Mediators Inflamm. 2012;2012:248574
references: 22685372
references: Endocrinology. 2007 Nov;148(11):5323-30
references: 17717053
references: Amino Acids. 2011 Oct;41(4):821-42
references: 20213444
references: Nat Med. 2007 Sep;13(9):1042-9
references: 17767165
references: World J Gastroenterol. 2008 Jun 28;14(24):3866-71
references: 18609711
references: Genomics. 1995 Feb 10;25(3):638-43
references: 7759097
references: CA Cancer J Clin. 2010 Sep-Oct;60(5):277-300
references: 20610543
references: Biochim Biophys Acta. 2008 Feb;1783(2):297-311
references: 18060880
references: FASEB J. 2005 Mar;19(3):467-9
references: 15642721
references: Amino Acids. 2011 Oct;41(4):773-80
references: 20182755
references: J Biol Chem. 2011 Dec 30;286(52):44845-54
references: 22016394
references: Commun Integr Biol. 2009;2(1):46-9
references: 19513264
references: Cancer Lett. 2008 Jun 18;264(2):209-17
references: 18334282
references: Mediators Inflamm. 2002 Jun;11(3):165-72
references: 12137245
references: Trends Immunol. 2003 Apr;24(4):155-8
references: 12697438
references: PLoS One. 2012;7(3):e34207
references: 22470535
references: Anticancer Res. 2003 May-Jun;23(3A):2043-51
references: 12894577
references: Gen Physiol Biophys. 2009;28 Spec No Focus:F55-64
references: 20093727
references: Int J Oncol. 2012 Jul;41(1):292-8
references: 22469784
references: Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2509-14
references: 9482916
references: Curr Opin Cell Biol. 2007 Apr;19(2):150-8
references: 17306971
references: Sci Signal. 2008 Nov 11;1(45):ra12
references: 19001663
references: Curr Cancer Drug Targets. 2008 Jun;8(4):243-52
references: 18537548
references: Microsc Res Tech. 2003 Apr 15;60(6):540-51
references: 12645002
references: Int J Oncol. 2005 Dec;27(6):1473-81
references: 16273201
references: J Cell Sci. 2008 Jan 15;121(Pt 2):234-45
references: 18187455
references: N Engl J Med. 2009 Dec 17;361(25):2449-60
references: 20018966
references: J Innate Immun. 2012;4(1):31-40
references: 21912088
references: Oncol Rep. 2001 May-Jun;8(3):591-6
references: 11295086
references: Med Sci Monit. 2012 Jul;18(7):BR273-80
references: 22739727
references: Science. 1998 Sep 4;281(5382):1509-12
references: 9727977
references: J Leukoc Biol. 2008 Jun;83(6):1484-92
references: 18339893
references: Med Oncol. 2000 Aug;17(3):183-8
references: 10962528
references: PLoS One. 2012;7(1):e30185
references: 22295074
references: Am J Pathol. 1999 Oct;155(4):1033-8
references: 10514384
references: Oncogene. 2004 Feb 12;23(6):1291-9
references: 14647409