Wnt-5a-Receptor Tyrosine Kinase-Like Orphan Receptor 2 Signaling Provokes Metastatic Colonization and Angiogenesis in...

Area of Science:

• Oncology
• Molecular Biology
• Cancer Signaling

Background:

• Clear cell renal cell carcinoma (ccRCC) is a significant health concern with unclear underlying molecular mechanisms.
• The Wnt-5a-ROR2 signaling pathway's role in ccRCC pathogenesis is not well understood.

Purpose of the Study:

• To investigate the prognostic value of Wnt-5a and ROR2 expression in ccRCC.
• To elucidate the functional impact of the Wnt-5a-ROR2 axis on ccRCC cell behavior and metastasis.
• To identify potential therapeutic targets for ccRCC.

Main Methods:

• Analysis of WNT5A and ROR2 expression in ccRCC cell lines and patient data.
• Investigating Wnt-5a regulation by epigenetic modifiers (5-azacytidine).
• Functional assays including cell migration, invasion, angiogenesis, and colonization after WNT5A/ROR2 knockdown.
• Gene expression profiling to identify downstream signaling alterations.
• Evaluating the effect of prunetin on Wnt-5a-ROR2 signaling and ccRCC cell phenotypes.

Main Results:

• Concurrent high WNT5A and ROR2 expression correlated with poor prognosis in ccRCC patients.
• Wnt-5a was upregulated in ccRCC cells and could be epigenetically modulated.
• WNT5A and ROR2 knockdown suppressed ccRCC cell migration, invasion, and metastasis in vitro and in vivo.
• Silencing WNT5A/ROR2 inhibited angiogenesis and endothelial cell function.
• Wnt-5a-ROR2 signaling alterations mimicked the metastasis-associated gene 1-β-catenin axis.
• Prunetin reversed Wnt-5a-ROR2 signaling, inhibiting ccRCC cell migration and proliferation.

Conclusions:

• The Wnt-5a-ROR2 axis plays a critical role in ccRCC progression, metastasis, and angiogenesis.
• Aberrant Wnt-5a-ROR2 signaling is a potential therapeutic target in ccRCC.
• Prunetin demonstrates potential as a precision medicine agent for ccRCC patients with activated Wnt-5a-ROR2 pathways.