title: Pancreatic cancer and hedgehog pathway signaling: new insights.
abstract: While several aberrant signaling pathways have been attributed to the formation and progression of pancreatic cancer, there is mounting evidence for the increased role of the Hedgehog (Hh) pathway in multiple aspects of pancreatic tumor development. The Hh pathway is a signaling cascade that plays an important role in cell patterning of multiple tissues and organs, including the development of the gastrointestinal system. While normal pancreatic tissue exhibits little Hh pathway activity, patients with pancreatic adenocarcinoma show high levels of Hh pathway signaling in both the tumor epithelia and the surrounding mesenchyme. Several recent studies have focused on this paracrine activation of Hh signaling in the tumor microenvironment and have provided evidence for how activation of this pathway may play roles in mediating cellular proliferation, metastasis, and resistance to therapy. Together, these findings present new insights into how modulation of this pathway may allow us to target multiple aspects of pancreatic tumor biology.
authors.affiliation: Department of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Dosch
authors.forename: Marina
authors.initials: M
authors.lastname: Pasca di Magliano
authors.forename: Diane M
authors.initials: DM
authors.lastname: Simeone
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D053823:Hedgehog Proteins / Q000502:physiology*; D006801:Humans; D051379:Mice; D014411:Neoplastic Stem Cells / Q000502:physiology; D010179:Pancreas / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000503:physiopathology*; D015398:Signal Transduction
chemical_list: D053823:Hedgehog Proteins
references.citation: Nature. 2006 Dec 7;444(7120):756-60
references.pmid: 17051156
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8
references.pmid: 12629218
references.citation: Gastroenterology. 2008 Jun;134(7):2080-90
references.pmid: 18549880
references.citation: Science. 2007 Jul 20;317(5836):337
references.pmid: 17641192
references.citation: Biochem Soc Trans. 2007 Nov;35(Pt 5):1347-51
references.pmid: 17956348
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):5103-8
references.pmid: 17372229
references.citation: Cancer Res. 2006 Jun 15;66(12):6063-71
references.pmid: 16778178
references.citation: Genes Dev. 1998 Jun 1;12(11):1705-13
references.pmid: 9620856
references.citation: Cancer Res. 2007 Jul 15;67(14):6981-6
references.pmid: 17638910
references.citation: Genes Dev. 2003 Dec 15;17(24):3112-26
references.pmid: 14681207
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10158-63
references.pmid: 17548814
references.citation: Cell. 1996 Jun 14;85(6):841-51
references.pmid: 8681379
references.citation: Cancer Res. 2007 Mar 1;67(5):2187-96
references.pmid: 17332349
references.citation: Nature. 2004 Oct 7;431(7009):707-12
references.pmid: 15361885
references.citation: Stem Cells. 2008 Feb;26(2):364-71
references.pmid: 17975224
references.citation: Nucleic Acids Res. 1988 Aug 25;16(16):7773-82
references.pmid: 3047672
references.citation: Nature. 2003 Oct 23;425(6960):846-51
references.pmid: 14520411
references.citation: Curr Biol. 2007 Jan 23;17(2):165-72
references.pmid: 17196391
references.citation: Cancer Res. 2008 Feb 1;68(3):918-26
references.pmid: 18245495
references.citation: Cancer Cell. 2004 Apr;5(4):375-87
references.pmid: 15093544
references.citation: Nature. 2003 Mar 20;422(6929):313-7
references.pmid: 12629553
references.citation: Curr Biol. 1997 Oct 1;7(10):801-4
references.pmid: 9368764
references.citation: Nat Med. 1997 Jul;3(7):730-7
references.pmid: 9212098
references.citation: Nature. 2004 Nov 18;432(7015):396-401
references.pmid: 15549107
references.citation: Nat Rev Cancer. 2003 Dec;3(12):903-11
references.pmid: 14737121
references.citation: Cell Stem Cell. 2007 Nov;1(5):555-67
references.pmid: 18371393
references.citation: Nature. 2003 Oct 23;425(6960):851-6
references.pmid: 14520413
references.citation: Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13036-41
references.pmid: 9789036
references.citation: Cell. 1988 May 20;53(4):549-54
references.pmid: 2453289
references.citation: J Clin Invest. 2007 Jan;117(1):50-9
references.pmid: 17200706
references.citation: Nat Rev Drug Discov. 2006 Dec;5(12):1026-33
references.pmid: 17139287
references.citation: Int J Clin Exp Pathol. 2008 Jan 01;1(4):306-16
references.pmid: 18787611
references.citation: Genes Dev. 2006 Nov 15;20(22):3161-73
references.pmid: 17114586
references.citation: Nature. 2008 Sep 18;455(7211):406-10
references.pmid: 18754008
references.citation: Cancer Res. 2006 Jul 15;66(14):7041-9
references.pmid: 16849549
references.citation: FASEB J. 2009 Jan;23(1):21-33
references.pmid: 18772349
references.citation: Genes Dev. 2009 Jan 1;23(1):24-36
references.pmid: 19136624
references.citation: Cancer Res. 2007 Feb 1;67(3):1030-7
references.pmid: 17283135
references.citation: PLoS One. 2008 Jun 18;3(6):e2428
references.pmid: 18560594
references.citation: Science. 2008 Sep 26;321(5897):1801-6
references.pmid: 18772397
references.citation: Clin Cancer Res. 2000 Aug;6(8):2969-72
references.pmid: 10955772
references.citation: PLoS Med. 2008 Dec 9;5(12):e239
references.pmid: 19071955
references.citation: Clin Cancer Res. 2008 Oct 1;14(19):5995-6004
references.pmid: 18829478
references.citation: Nat Genet. 2002 Jul;31(3):306-10
references.pmid: 12068298
references.citation: Gastroenterology. 2008 Aug;135(2):621-31
references.pmid: 18515092