Authors
Chengyu Wei, Xiangyu Liu, Shimin Hu, Xiaodie Shen, Yingli Liu, Xinxin Qin, Ye Zhou, Jianqi Zheng, Bingke Tian, Jingfang Hong, Yongxia Song, Di Wang, Linlin Peng, Jinxia Ding, Fang Wang, Hui Zhang, Shihao Zhang, Huan Qiu
Published in
Cancer science. Jul 21, 2026. Epub Jul 21, 2026.
Abstract
Angiogenesis is essential for tumor progression, MEN1 gene encodes the menin protein, which is known as a tumor suppressor in lung tissue. Our previous study have shown that vascular density is significantly increased in menin-deficient lung cancer, suggesting that menin deficiency may promote the malignant progression of lung cancer by enhancing angiogenesis. However, whether menin play an important role in angiogenesis of lung cancer and the underlying mechanisms remain unclear. In this study, lung-specific KrasG12D mutation induced mouse lung cancer model, clinical human lung cancer tissues, lung cancer and vascular endothelial cell lines were utilized, RNA-seq, ATAC-seq, ChIP, tube formation, sprouting, invasion and migration experiments were applied to investigate the role and mechanism of MEN1 in lung cancer angiogenesis. The result show menin were negatively related to angiogenesis markers and phenotype. Menin deficiency indirectly upregulates MMP10 transcription through activation of the transcription factor JunD. The expression of MMP10 further activates the EGFR receptor in vascular endothelial cells, thereby initiating the AKT/ERK signaling pathway. Inhibition MMP10 reversed menin low expression induce angiogenic phenotype and tumor progress. In conclusion, menin deficiency promotes angiogenesis through upregulates MMP10, targeting MMP10 with inhibitor represent an effective anti-angiogenic strategy for treating MEN1-deficient lung cancer.
PMID:
42479119
Bibliographic data and abstract were imported from PubMed on 21 Jul 2026.
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