AATF suppresses apoptosis, promotes proliferation and is critical for Kras-driven lung cancer.
Oncogene
; 37(11): 1503-1518, 2018 03.
Article
in En
| MEDLINE
| ID: mdl-29321668
ABSTRACT
A fundamental principle in malignant tranformation is the ability of cancer cells to escape the naturally occurring cell-intrinsic responses to DNA damage. Tumors progress despite the accumulation of DNA lesions. However, the underlying mechanisms of this tolerance to genotoxic stress are still poorly characterized. Here, we show that replication stress occurs in Kras-driven murine lung adenocarcinomas, as well as in proliferating murine embryonic and adult tissues. We identify the transcriptional regulator AATF/CHE-1 as a key molecule to sustain proliferative tissues and tumor progression in parts by inhibiting p53-driven apoptosis in vivo. In an autochthonous Kras-driven lung adenocarcinoma model, deletion of Aatf delayed lung cancer formation predominantly in a p53-dependent manner. Moreover, targeting Aatf in existing tumors through a dual recombinase strategy caused a halt in tumor progression. Taken together, these data suggest that AATF may serve as a drug target to treat KRAS-driven malignancies.
Full text:
1
Database:
MEDLINE
Main subject:
Repressor Proteins
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Proto-Oncogene Proteins p21(ras)
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Apoptosis
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Cell Proliferation
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Apoptosis Regulatory Proteins
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Adenocarcinoma of Lung
/
Lung Neoplasms
Type of study:
Prognostic_studies
Limits:
Animals
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Female
/
Humans
/
Male
Language:
En
Year:
2018
Type:
Article