神经肽1
旁分泌信号
旁侵犯
自分泌信号
前列腺癌
癌症研究
单胺氧化酶A
生物
癌症
单胺氧化酶
内科学
医学
受体
酶
血管内皮生长因子受体
血管内皮生长因子
生物化学
作者
Yin Liu,Jingjing Li,Jing Wang,Tianjie Pu,Jing Wei,Qinlong Li,Bainan Wu
出处
期刊:Oncogene
[Springer Nature]
日期:2021-01-08
卷期号:40 (7): 1362-1374
被引量:48
标识
DOI:10.1038/s41388-020-01615-2
摘要
Perineural invasion (PNI), a pathologic feature defined as cancer cell invasion in, around, and through nerves, is an indicator of poor prognosis and survival in prostate cancer (PC). Despite widespread recognition of the clinical significance of PNI, the molecular mechanisms are largely unknown. Here, we report that monoamine oxidase A (MAOA) is a clinically and functionally important mediator of PNI in PC. MAOA promotes PNI of PC cells in vitro and tumor innervation in an orthotopic xenograft model. Mechanistically, MAOA activates SEMA3C in a Twist1-dependent transcriptional manner, which in turn stimulates cMET to facilitate PNI via autocrine or paracrine interaction with coactivated PlexinA2 and NRP1. Furthermore, MAOA inhibitor treatment effectively reduces PNI of PC cells in vitro and tumor-infiltrating nerve fiber density along with suppressed xenograft tumor growth and progression in mice. Collectively, these findings characterize the contribution of MAOA to the pathogenesis of PNI and provide a rationale for using MAOA inhibitors as a targeted treatment for PNI in PC.
科研通智能强力驱动
Strongly Powered by AbleSci AI