Pancreatic fibroblasts smoothen their activities via AKT-GLI2-TGFα.
Pancreatic stromal fibroblasts provide structural support. Activated fibroblasts are critical in the tumor microenvironment. In this issue of Genes & Development, Liu and colleagues (pp. 1943-1955) unravel the finding that depletion of Smoothened (Smo) in pancreatic stromal fibroblasts results in AKT activation and noncanonical GLI2 activation with subsequent TGFα secretion, activation of EGFR in pancreatic epithelial cells, and augmentation of acinar-ductal metaplasia. Additionally, Smo-mediated signaling has proproliferative effects on pancreatic tumor cells.
Division of Gastroenterology, Department of Medicine, Department of Genetics, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Anil K
AK
Rustgi
D005347:Fibroblasts; D053823:Hedgehog Proteins / Q000235:genetics; D008679:Metaplasia; D010179:Pancreas; D010190:Pancreatic Neoplasms / Q000235:genetics; D015398:Signal Transduction; D016211:Transforming Growth Factor alpha
D053823:Hedgehog Proteins; D016211:Transforming Growth Factor alpha
AKT signaling; EGFR signaling; acinar-to-ductal metaplasia; hedgehog signaling; stromal fibroblast
Genes Dev. 2013 Feb 1;27(3):288-300
23355395
Cancer Cell. 2014 Jun 16;25(6):735-47
24856585
Genes Dev. 2016 Sep 1;30(17 ):1943-55
27633013
Genes Dev. 1998 Jun 1;12(11):1705-13
9620856
Cancer Cell. 2014 Jun 16;25(6):719-34
24856586
Nature. 2003 Oct 23;425(6960):851-6
14520413
Proc Natl Acad Sci U S A. 2014 Jul 29;111(30):E3091-100
25024225
Genes Dev. 2006 Nov 15;20(22):3161-73
17114586
Development. 2000 Nov;127(22):4905-13
11044404
Genes Dev. 2009 Jan 1;23 (1):24-36
19136624