High IGFL2 regulates ovarian cancer progression and the tumor immune microenvironment via the Warburg effect.

This study aimed to explore the role and mechanism of insulin-like growth factor-like family member 2 (IGFL2) in ovarian cancer (OC) metastasis. Specifically, we focused on how IGFL2 regulates tumor cell energy metabolism and influences macrophage polarization to promote ovarian cancer metastasis. By conducting in vitro and in vivo experiments to elucidate the biological functions of IGFL2, this study aiming to identify new therapeutic targets for ovarian cancer treatment and provide a more effective treatment strategy. Our study revealed that the expression of IGFL2 was substantially upregulated in ovarian cancer metastases, and its high expression was positively correlated with the malignancy and metastatic potential of ovarian cancer. IGFL2 knockdown promoted mitochondrial oxidative phosphorylation and inhibited the Warburg effect, evidenced by increased oxygen consumption rate (OCR) and ATP production, and decreased glycolytic enzyme expression and lactate secretion. Concurrently, IGFL2 promoted M2 macrophage polarization via the STAT1/STAT6 signaling pathway, increasing the proportion of CD11b + CD206 + M2 cells and suppressing M1 polarization. In vivo, IGFL2 knockdown significantly inhibited tumor growth and metabolic reprogramming in xenograft models.These findings demonstrate that IGFL2 promotes OC metastasis through a dual mechanism: regulating metabolic reprogramming (Warburg effect) and influencing tumor-associated macrophage (TAM) polarization.