IGFL2 suppresses gastric cancer cell sensitivity to docetaxel by activating the Toll-like receptor signaling pathway

Docetaxel (DTX) resistance limits therapeutic efficacy in gastric cancer (GC). Through RNA sequencing of DTX-resistant GC cells, we identified insulin-like growth factor-like family member 2 (IGFL2) as a key upregulated gene. We demonstrate that IGFL2 overexpression enhances GC cell proliferation, migration, and invasion while suppressing apoptosis, thereby reducing DTX sensitivity. Mechanistically, IGFL2 directly binds the Toll-like receptor 4 (TLR4) promoter, activating the TLR4/MyD88/p65 pathway and upregulating drug efflux pumps MDR1 and BCRP. Knockdown of IGFL2 resensitizes resistant cells to DTX both in vitro and in mouse xenograft models. These findings establish IGFL2 as a regulator of DTX resistance via TLR4 signaling, suggesting its relevance as a therapeutic target for overcoming chemoresistance in GC.