A loss-of-function mutation in PTCH1 suggests a role for autocrine hedgehog signaling in colorectal tumorigenesis

Content Provider	Semantic Scholar
Author	Chung, Jon H. Bunz, Fred
Copyright Year	2013
Abstract	Hedgehog (Hh) signaling is largely suppressed in the normal differentiated tissues of the adult but activated in many cancers. The Hh pathway can either be activated by the expression of Hh ligands, or by mutations that cause constitutive, ligand-independent signaling. Colorectal cancer cells frequently express Hh ligands that are believed to exert paracrine effects on the stromal component of the tumor. Evidence for a more direct role of Hh signaling on the growth and evolution of colorectal cancer cell clones has been lacking. Here, we report a loss-of-function mutation of PTCH1, a tumor suppressor in the Hh pathway, in a colorectal cancer that exhibits transcriptional upregulation of the downstream Hh gene GLI1. This finding demonstrates that autocrine Hh signaling can provide a selective advantage to evolving tumors that arise in the colorectal epithelia, and suggests a definable group of colorectal cancer patients that could derive enhanced benefit from Hh pathway inhibitors.
Starting Page	2208
Ending Page	2211
Page Count	4
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&op=download&page=article&path%5B%5D=1651&path%5B%5D=1811
PubMed reference number	24368541v1
Volume Number	4
Journal	Oncotarget
Language	English
Access Restriction	Open
Subject Keyword	Body tissue Carcinogenesis Colorectal Carcinoma Erinaceidae Exhibits as Topic GLI1 protein, human Have Trouble Finding Right Words to Express Myself Ligands Malignant Neoplasms Mutation Nephroblastoma Non-Small Cell Lung Carcinoma PTCH1 gene Patients Transcription, Genetic autocrine omacetaxine mepesuccinate physical hard work
Content Type	Text
Resource Type	Article