MEN1 deficiency leads to neuroendocrine differentiation of lung cancer and disrupts the DNA damage response
Authors:
Open Access
- 21 February 2020
- journal article
- research article
- Published by Springer Nature in Nature Communications
- Vol. 11 (1) , 1-12
Abstract
The MEN1 gene, a tumor suppressor gene that encodes the protein menin, is mutated at high frequencies in neuroendocrine (NE) tumors; however, the biological importance of this gene in NE-type lung cancer in vivo remains unclear. Here, we established an ATII-specific KrasG12D/+/Men1−/− driven genetically engineered mouse model and show that deficiency of menin results in the accumulation of DNA damage and antagonizes oncogenic Kras-induced senescence and the epithelial-to-mesenchymal transition during lung tumorigenesis. The loss of menin expression in certain human primary lung cancers correlates with elevated NE profiles and reduced overall survival.Keywords
Funding Information
- National Natural Science Foundation of China (81572778, U1605224)
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