Signaling and Mechanistic Insights into Folate Binding Protein-Induced Cytotoxicity in KB Cancer Cells

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Folate binding protein (FBP) is the soluble form of folate receptor (FR).
• Previous studies showed FBP inhibits tumor growth and induces apoptosis in cancer cells.
• The precise mechanisms underlying FBP's cytotoxic effects require further investigation.

Purpose of the Study:

• To elucidate the molecular mechanisms of FBP-induced cytotoxicity and apoptosis in FR-overexpressing KB cancer cells.
• To identify key genes and pathways affected by FBP treatment.
• To understand the role of folate deprivation in FBP-mediated cell death.

Main Methods:

• Next-generation sequencing (NGS) for RNA sequencing and gene expression profiling.
• Bioinformatics analysis of transcriptomics data.
• Immunofluorescence analysis and TUNEL assay to examine protein expression and DNA damage.

Main Results:

• FBP treatment altered the expression of genes involved in epithelial to mesenchymal transition (EMT), inflammation, and apoptosis pathways (e.g., Snail1, MCP-1, ZFP36, HOXA9).
• FBP exposure led to DNA breakage and induced caspase-mediated apoptosis in KB cells.
• Transcriptomic and functional data support FBP-mediated folate deprivation as the mechanism of cytotoxicity.

Conclusions:

• FBP induces cytotoxicity and apoptosis in FR-overexpressing KB cancer cells through folate deprivation.
• Altered gene expression in EMT, inflammatory, and apoptosis pathways contributes to FBP's anti-cancer effects.
• The findings provide insights into FBP's mechanism of action for potential therapeutic strategies against FR-overexpressing cancers.