title: HIG2 promotes colorectal cancer progression via hypoxia-dependent and independent pathways.
abstract: HIG2 (hypoxia-inducible gene 2) is a biomarker of hypoxia and elevated in several cancers. Here, we show that HIG2 also upregulated HIF-1α expression under hypoxic conditions and enhanced AP-1 expression under normoxic conditions, which affects colorectal cancer cell survival. Importantly, over-expression of HIG2 promoted tumor growth by suppressing apoptosis in a mouse orthotopic model. These results are likely relevant to human disease since we found that the expression of HIG2 is gradually elevated as tumors progress. Collectively, these findings suggest that HIG2 plays an important role in promoting colorectal cancer growth in hypoxia-dependent and independent manners.
authors.affiliation: Departments of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, United States.
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Dingzhi
authors.initials: D
authors.lastname: Wang
authors.forename: Yun-Yong
authors.initials: YY
authors.lastname: Park
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katoh
authors.forename: Ofer
authors.initials: O
authors.lastname: Margalit
authors.forename: Michal
authors.initials: M
authors.lastname: Sheffer
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.forename: Vijaykumar R
authors.initials: VR
authors.lastname: Holla
authors.forename: Ju-Seog
authors.initials: JS
authors.lastname: Lee
authors.forename: Raymond N
authors.initials: RN
authors.lastname: DuBois
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D019073:HT29 Cells; D064593:Heterografts / Q000473:pathology; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000235:genetics
chemical_list: C497442:HIF1A protein, human; C405620:HILPDA protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009363:Neoplasm Proteins
keywords: Colorectal cancer; HIF-1α; HIG2; Hypoxia; Normoxia; Survival
references.citation: Anticancer Res. 2001 Nov-Dec;21(6B):4317-24
references.pmid: 11908686
references.citation: Cancer Cell. 2011 Aug 16;20(2):214-28
references.pmid: 21840486
references.citation: Cell Cycle. 2007 Mar 15;6(6):656-9
references.pmid: 17361105
references.citation: Bioinformatics. 2004 Nov 1;20(16):2778-86
references.pmid: 15166021
references.citation: Cancer Res. 2005 Apr 1;65(7):2520-5
references.pmid: 15805242
references.citation: Cancer Res. 2010 Jan 15;70(2):813-23
references.pmid: 20068160
references.citation: Am J Respir Cell Mol Biol. 2008 Mar;38(3):251-5
references.pmid: 17932373
references.citation: Clin Cancer Res. 2000 Feb;6(2):480-7
references.pmid: 10690527
references.citation: Eur J Gynaecol Oncol. 2011;32(2):146-9
references.pmid: 21614900
references.citation: Cell Cycle. 2010 Jul 15;9(14):2749-63
references.pmid: 20603601
references.citation: FASEB J. 2010 Nov;24(11):4443-58
references.pmid: 20624928
references.citation: Nat Rev Cancer. 2003 Nov;3(11):859-68
references.pmid: 14668816
references.citation: J Steroid Biochem Mol Biol. 2005 Dec;97(4):328-41
references.pmid: 16157482
references.citation: Int J Biochem Cell Biol. 2010 Jul;42(7):1061-5
references.pmid: 20348011
references.citation: Cell Signal. 2005 Jan;17(1):1-9
references.pmid: 15451019
references.citation: Surg Oncol. 2007 Dec;16 Suppl 1:S25-7
references.pmid: 18023174
references.citation: Int J Gynecol Cancer. 2010 Feb;20(2):220-6
references.pmid: 20134266
references.citation: Inflammopharmacology. 2005;13(1-3):113-25
references.pmid: 16259733
references.citation: Int J Biochem Mol Biol. 2012;3(2):165-78
references.pmid: 22773957
references.citation: Nat Rev Cancer. 2011 Dec 15;12(1):9-22
references.pmid: 22169972
references.citation: Cancer Res. 2010 May 15;70(10):4054-63
references.pmid: 20442290
references.citation: J Pathol. 2010 Jun;221(2):125-38
references.pmid: 20225241
references.citation: Curr Cancer Drug Targets. 2007 Jun;7(4):317-24
references.pmid: 17979626
references.citation: Cancer Res. 2005 Jun 1;65(11):4817-26
references.pmid: 15930302