Recurrent somatic mutation of FAT1 in multiple human cancers leads to aberrant Wnt activation.
Nat Genet
; 45(3): 253-61, 2013 Mar.
Article
in En
| MEDLINE
| ID: mdl-23354438
ABSTRACT
Aberrant Wnt signaling can drive cancer development. In many cancer types, the genetic basis of Wnt pathway activation remains incompletely understood. Here, we report recurrent somatic mutations of the Drosophila melanogaster tumor suppressor-related gene FAT1 in glioblastoma (20.5%), colorectal cancer (7.7%), and head and neck cancer (6.7%). FAT1 encodes a cadherin-like protein, which we found is able to potently suppress cancer cell growth in vitro and in vivo by binding ß-catenin and antagonizing its nuclear localization. Inactivation of FAT1 via mutation therefore promotes Wnt signaling and tumorigenesis and affects patient survival. Taken together, these data strongly point to FAT1 as a tumor suppressor gene driving loss of chromosome 4q35, a prevalent region of deletion in cancer. Loss of FAT1 function is a frequent event during oncogenesis. These findings address two outstanding issues in cancer biology the basis of Wnt activation in non-colorectal tumors and the identity of a 4q35 tumor suppressor.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cadherins
/
Drosophila Proteins
/
Drosophila melanogaster
/
Wnt Signaling Pathway
/
Neoplasms
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Nat Genet
Journal subject:
GENETICA MEDICA
Year:
2013
Document type:
Article
Affiliation country:
United States
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
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US
/
USA