Hypoxia-Induced VGF Promotes Cell Migration and Invasion in Prostate Cancer via the PI3K/Akt Axis.

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Metastasis is a primary cause of prostate cancer (PCa) mortality.
• VGF nerve growth factor inducible (VGF) has been implicated in tumor invasion and metastasis.

Purpose of the Study:

• To investigate VGF expression in PCa.
• To elucidate the mechanisms by which VGF influences PCa progression, invasion, and metastasis.

Main Methods:

• VGF expression was modulated in PCa cell lines (22Rv1, C4-2) using shRNA and overexpression techniques.
• Quantitative PCR and Western blot analyzed VGF mRNA and protein levels.
• In vitro (Transwell, scratch assays) and in vivo (nude mouse model) experiments assessed cell invasion and metastasis.
• The role of the PI3K/Akt pathway and hypoxia-inducible factor 1-alpha (HIF-1α) was examined.

Main Results:

• VGF was abnormally expressed in PCa tissues and plasma, with VGF knockdown suppressing metastasis.
• VGF promoted PCa cell invasion and metastasis via the PI3K/Akt signaling pathway.
• VGF knockdown enhanced the efficacy of docetaxel in inhibiting PCa metastasis.
• Hypoxia increased VGF and HIF-1α levels, correlating with poor PCa prognosis.

Conclusions:

• VGF drives PCa invasive metastasis by activating the PI3K/Akt pathway.
• Targeting VGF presents a potential therapeutic strategy for metastatic prostate cancer.