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MAOA promotes prostate cancer cell perineural invasion through SEMA3C/PlexinA2/NRP1-cMET signaling
- Source :
- Oncogene
- Publication Year :
- 2020
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Male
Cancer Research
Cell signaling
Monoamine Oxidase Inhibitors
Perineural invasion
Nerve Tissue Proteins
Receptors, Cell Surface
Semaphorins
Article
03 medical and health sciences
Paracrine signalling
Prostate cancer
Mice
0302 clinical medicine
Cell Line, Tumor
Neuropilin 1
Genetics
medicine
Animals
Humans
Neoplasm Invasiveness
Autocrine signalling
Molecular Biology
Monoamine Oxidase
Cell Proliferation
biology
Twist-Related Protein 1
Nuclear Proteins
Prostatic Neoplasms
Proto-Oncogene Proteins c-met
medicine.disease
Neuropilin-1
030104 developmental biology
030220 oncology & carcinogenesis
Cancer cell
Cancer research
biology.protein
Heterografts
Monoamine oxidase A
Signal Transduction
Subjects
Details
- ISSN :
- 14765594
- Volume :
- 40
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....d20be568580473a133f9515ee6549cb6