SSeCKS/AKAP12 induces repulsion between human prostate cancer and microvessel endothelial cells through the activation of Semaphorin 3F
Wen Xie1, Wei Su2, Lijuan Zhang3
1Orthopedic Institute of Henan Province, Luoyang, Henan 471002, China.
Abstract:
Metastasis remains the primary cause of prostate cancer related death. Cancer cells need to contact endothelial cells and disrupt endothelial junctions to cross the endothelium for invasion and metastasis. The suppression of heterotypic repulsion between cancer and endothelial cells allows cancer cells to invade into the surrounding tissue. Here, we demonstrate that SSeCKS/AKAP12 induced repulsion between human prostate cancer and microvessel endothelial cells, which was mediated by an angiogenesis inhibitor Semaphorin 3F. Moreover, we examined AKAP12 and Semaphorin 3F mRNA expression in 42 prostate cancer and 30 benign prostatic hyperplasia tissue samples, and found that the expression of AKAP12 and Semaphorin 3F mRNA was inversely associated with the degree of aggressiveness of prostate cancer cells and tissues. An ordinal logistic regression analysis indicates that there is a positive association between the expression of AKAP12 and Semaphorin 3F in prostate cancer, suggesting that the activation of Semaphorin 3F by SSeCKS/AKAP12 may be involved in prostate cancer progression and metastasis.
Insights
Prostate cancer cells invade by suppressing repulsion with endothelial cells. SSeCKS/AKAP12 promotes repulsion via Semaphorin 3F, inhibiting metastasis and indicating a potential therapeutic target.
Area of Science:
- Oncology
- Cell Biology
- Molecular Medicine
Background:
- Prostate cancer metastasis is a major cause of cancer-related death.
- Cancer cell invasion requires interaction with and disruption of endothelial cells.
- Suppression of repulsion between cancer and endothelial cells facilitates invasion.
Purpose of the Study:
- To investigate the role of SSeCKS/AKAP12 in mediating repulsion between prostate cancer and endothelial cells.
- To explore the involvement of Semaphorin 3F in this process.
- To correlate the expression of AKAP12 and Semaphorin 3F with prostate cancer aggressiveness.
Main Methods:
- Investigated SSeCKS/AKAP12-induced repulsion between human prostate cancer and microvessel endothelial cells.
- Examined AKAP12 and Semaphorin 3F mRNA expression in prostate cancer and benign prostatic hyperplasia tissues.
- Utilized ordinal logistic regression analysis to assess associations between gene expression and cancer aggressiveness.
Main Results:
- SSeCKS/AKAP12 induced repulsion between prostate cancer and endothelial cells, mediated by Semaphorin 3F.
- AKAP12 and Semaphorin 3F mRNA expression were inversely associated with prostate cancer aggressiveness.
- A positive association was found between AKAP12 and Semaphorin 3F expression in prostate cancer.
Conclusions:
- SSeCKS/AKAP12-induced Semaphorin 3F activation may inhibit prostate cancer cell invasion and metastasis.
- Reduced expression of AKAP12 and Semaphorin 3F correlates with increased prostate cancer aggressiveness.
- Targeting the SSeCKS/AKAP12-Semaphorin 3F pathway could offer a therapeutic strategy for prostate cancer.
