Back to the drawing board: Re-thinking the role of GLI1 in pancreatic carcinogenesis

Martin E. Fernandez-Zapico; Tara L. Hogenson; Matthias Lauth; Marina Pasca diMagliano

doi:10.12688/f1000research.5324.2

Back to the drawing board: Re-thinking the role of GLI1 in pancreatic carcinogenesis

Martin E. Fernandez-Zapico, Tara L. Hogenson, Matthias Lauth, Marina Pasca diMagliano

Oncology

Research output: Contribution to journal › Review article › peer-review

1 Scopus citations

Abstract

Aberrant activation of the transcription factor GLI1, a central effector of the Hedgehog (HH) pathway, is associated with several malignancies, including pancreatic ductal adenocarcinoma (PDAC), one of most deadly human cancers. GLI1 has been described as an oncogene in PDAC, making it a promising target for drug therapy. Surprisingly, clinical trials targeting HH/GLI1 axis in advanced PDAC were unsuccessful, leaving investigators questioning the mechanism behind these failures. Recent evidence suggests the loss of GLI1 in the later stages of PDAC may actually accelerate disease. This indicates GLI1 may play a dual role in PDAC, acting as an oncogene in the early stages of disease and a tumor-suppressor in the late stages.

Original language	English (US)
Article number	238
Journal	F1000Research
Volume	3
DOIs	https://doi.org/10.12688/f1000research.5324.2
State	Published - 2016

Keywords

Carcinogenesis
GLI1
HH
Hedgehog
PDAC
Pancreatic Cancer
Pancreatic ductal adenocarcinoma

ASJC Scopus subject areas

General Immunology and Microbiology
General Pharmacology, Toxicology and Pharmaceutics
General Biochemistry, Genetics and Molecular Biology

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10.12688/f1000research.5324.2

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title = "Back to the drawing board: Re-thinking the role of GLI1 in pancreatic carcinogenesis",

abstract = "Aberrant activation of the transcription factor GLI1, a central effector of the Hedgehog (HH) pathway, is associated with several malignancies, including pancreatic ductal adenocarcinoma (PDAC), one of most deadly human cancers. GLI1 has been described as an oncogene in PDAC, making it a promising target for drug therapy. Surprisingly, clinical trials targeting HH/GLI1 axis in advanced PDAC were unsuccessful, leaving investigators questioning the mechanism behind these failures. Recent evidence suggests the loss of GLI1 in the later stages of PDAC may actually accelerate disease. This indicates GLI1 may play a dual role in PDAC, acting as an oncogene in the early stages of disease and a tumor-suppressor in the late stages.",

keywords = "Carcinogenesis, GLI1, HH, Hedgehog, PDAC, Pancreatic Cancer, Pancreatic ductal adenocarcinoma",

author = "Fernandez-Zapico, {Martin E.} and Hogenson, {Tara L.} and Matthias Lauth and {Pasca diMagliano}, Marina",

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year = "2016",

doi = "10.12688/f1000research.5324.2",

language = "English (US)",

volume = "3",

journal = "F1000Research",

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T1 - Back to the drawing board

T2 - Re-thinking the role of GLI1 in pancreatic carcinogenesis

AU - Fernandez-Zapico, Martin E.

AU - Hogenson, Tara L.

AU - Lauth, Matthias

AU - Pasca diMagliano, Marina

PY - 2016

Y1 - 2016

N2 - Aberrant activation of the transcription factor GLI1, a central effector of the Hedgehog (HH) pathway, is associated with several malignancies, including pancreatic ductal adenocarcinoma (PDAC), one of most deadly human cancers. GLI1 has been described as an oncogene in PDAC, making it a promising target for drug therapy. Surprisingly, clinical trials targeting HH/GLI1 axis in advanced PDAC were unsuccessful, leaving investigators questioning the mechanism behind these failures. Recent evidence suggests the loss of GLI1 in the later stages of PDAC may actually accelerate disease. This indicates GLI1 may play a dual role in PDAC, acting as an oncogene in the early stages of disease and a tumor-suppressor in the late stages.

AB - Aberrant activation of the transcription factor GLI1, a central effector of the Hedgehog (HH) pathway, is associated with several malignancies, including pancreatic ductal adenocarcinoma (PDAC), one of most deadly human cancers. GLI1 has been described as an oncogene in PDAC, making it a promising target for drug therapy. Surprisingly, clinical trials targeting HH/GLI1 axis in advanced PDAC were unsuccessful, leaving investigators questioning the mechanism behind these failures. Recent evidence suggests the loss of GLI1 in the later stages of PDAC may actually accelerate disease. This indicates GLI1 may play a dual role in PDAC, acting as an oncogene in the early stages of disease and a tumor-suppressor in the late stages.

KW - Carcinogenesis

KW - GLI1

KW - HH

KW - Hedgehog

KW - PDAC

KW - Pancreatic Cancer

KW - Pancreatic ductal adenocarcinoma

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DO - 10.12688/f1000research.5324.2

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JO - F1000Research

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Back to the drawing board: Re-thinking the role of GLI1 in pancreatic carcinogenesis

Abstract

Keywords

ASJC Scopus subject areas

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