WIF1 can effectively co-regulate pro-apoptotic activity through the combination with DKK1

Area of Science:

• Oncology
• Molecular Biology
• Cell Signaling

Background:

• Wnt inhibitory factor-1 (WIF1) is a Wnt antagonist that binds Frizzled receptors, inhibiting Wnt/β-catenin signaling.
• WIF1, in conjunction with Dickkopf-1 (DKK1), modulates apoptotic and anti-apoptotic protein expression.

Purpose of the Study:

• To investigate the role of WIF1 in apoptosis, cell cycle regulation, and angiogenesis.
• To elucidate the molecular mechanisms underlying WIF1's tumor-suppressive functions, particularly its interaction with the PI3K/Akt/mTOR pathway.

Main Methods:

• Co-transfection of cells with WIF1 and DKK1.
• Analysis of protein and gene expression (p53, p21, c-Myc, Bcl-2).
• Assessment of the PI3K/Akt/mTOR signaling pathway components' phosphorylation status.

Main Results:

• WIF1 and DKK1 increased p53 and p21 expression while decreasing c-Myc and Bcl-2.
• WIF1 suppressed tumor growth by inhibiting angiogenesis via targeting the PI3K/Akt/mTOR pathway.
• WIF1 reduced VEGF-induced phosphorylation of key signaling molecules including PDK1, mTOR, TSC-2, GSK-3β, and p70S6K.

Conclusions:

• WIF1 acts as a tumor suppressor by promoting apoptosis and inhibiting angiogenesis.
• WIF1's targeting of the PI3K/Akt/mTOR pathway is crucial for its anti-cancer effects.
• WIF1 represents a promising molecular target for the treatment of various malignant cancers.