CEP70 in Prostate Cancer: A Novel Mechanism of Angiogenesis and Metastasis through Upregulation of Vascular Endothelial Growth Factor A Expression.

Abstract

Background: This study aims to investigate centrosomal protein 70 (CEP70) in prostate cancer and its effects on angiogenesis and tumour metastasis and elucidate its molecular mechanisms.

Methods: We evaluated CEP70 and Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) in tissue samples from patients with prostate cancer by immunohistochemistry. In vitro experiments included overexpressing CEP70 through transfection and assessing its impact on human umbilical vein endothelial cells (HUVECs). Intervention experiments with an NF-κB pathway inhibitor were conducted to verify the mechanism. Finally, the effects of CEP70 on tumour growth, angiogenesis and metastasis were examined in a nude mouse model.

Results: CEP70 was significantly overexpressed in prostate cancer tissues compared with that in adjacent normal tissues (p < 0.001). In vitro experiments demonstrated that CEP70 overexpression promoted HUVEC migration (p < 0.001), invasion (p < 0.001) and tube formation (p < 0.05). CEP70 significantly upregulated VEGFA expression in prostate cancer cells at messenger RNA (mRNA) (p < 0.001) and protein levels (p < 0.05). VEGFA knockdown experiments confirmed CEP70 as an essential cytokine for CEP70-induced angiogenesis (p < 0.01). Mechanistically, CEP70 promoted VEGFA expression by activating the NF-κB signalling pathway, as evidenced by the reversal of CEP70-induced effects upon treatment with the NF-κB inhibitor BAY11-7082 (p < 0.01).

Conclusions: CEP70 promotes tumour angiogenesis and metastasis by upregulating VEGFA through NF-κB pathway activation.