MEN1 deficiency leads to neuroendocrine differentiation of lung cancer and disrupts the DNA damage response
Huan Qiu, Bangming Jin, Zhanfeng Wang, Bin Xu, Qi‐Fan Zheng, Li Zhang, Ling-Yu Zhu, Shuang Shi, Jun-Bo Yuan, Xiao Lin, Shu-Bin Gao, Guang‐Hui Jin
Abstract
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 Kras G12D/+ / 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.