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rFIP-GMI Suppresses IGF-1–Induced Invasion and Migration in Breast Cancer Cells via PI3K/Akt/β-Catenin Inhibition

Summary

Researchers found that a protein from a medicinal mushroom called Ganoderma microsporum can fight aggressive breast cancer by blocking a cellular pathway that helps cancer cells spread. The protein works by stopping the activation of key molecules (PI3K and Akt) that cancer cells use to invade surrounding tissues and migrate to other parts of the body. By blocking this pathway, the mushroom protein also prevents another molecule called β-catenin from entering the cell nucleus, where it would trigger genes that promote cancer growth and spread.

Background

Triple-negative breast cancer (TNBC) is an aggressive subtype with high metastatic potential and limited therapeutic options. Insulin-like growth factor-1 (IGF-1) promotes breast cancer progression through the PI3K/Akt pathway, enhancing invasion and migration via epithelial-mesenchymal transition (EMT). Recombinant fungal immunomodulatory protein from Ganoderma microsporum (rFIP-GMI) possesses anti-inflammatory and anticancer activities, but its role in suppressing tumor invasion and migration remains unclear.

Objective

This study investigated the molecular mechanism of rFIP-GMI in suppressing IGF-1-induced invasion and migration in TNBC cell lines (Hs578T and MDA-MB-231) through modulation of the PI3K/Akt/β-catenin signaling pathway.

Results

rFIP-GMI significantly inhibited IGF-1-induced invasion and migration by suppressing PI3K and Akt phosphorylation, thereby activating GSK3β and promoting β-catenin phosphorylation and degradation. This led to reduced nuclear β-catenin accumulation and downregulation of oncogenic targets (c-Myc, cyclin D1, MMP-9). MG132 confirmed that rFIP-GMI stabilizes cytoplasmic phosphorylated β-catenin and blocks nuclear translocation.

Conclusion

rFIP-GMI inhibits IGF-1-driven invasion and migration in TNBC by inactivating the PI3K/Akt/β-catenin axis, demonstrating its potential as a therapeutic agent for this aggressive cancer subtype. Additional validation using in vivo xenograft models and exploration of crosstalk with other oncogenic pathways is warranted.
  • Published in:Drug Development Research,
  • Study Type:In Vitro Experimental Study,
  • Source: PMID: 41294378, DOI: 10.1002/ddr.70202
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