Chen Zhizai, Song Dalong, Huang Shuting, Chao Jinyu, Huang Junhong, Luo Ming, He Shanyang
School of Medicine, South China University of Technology, Guangzhou, 510006, People's Republic of China.
Department of Gynecology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People's Republic of China.
Mol Cell Biochem. 2025 Jun 23. doi: 10.1007/s11010-025-05328-6.
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.
本研究旨在探讨胰岛素样生长因子样家族成员2（IGFL2）在卵巢癌（OC）转移中的作用及机制。具体而言，我们关注IGFL2如何调节肿瘤细胞能量代谢并影响巨噬细胞极化以促进卵巢癌转移。通过进行体外和体内实验来阐明IGFL2的生物学功能，本研究旨在确定卵巢癌治疗的新靶点并提供更有效的治疗策略。我们的研究表明，IGFL2在卵巢癌转移灶中的表达显著上调，其高表达与卵巢癌的恶性程度和转移潜能呈正相关。IGFL2基因敲低促进线粒体氧化磷酸化并抑制瓦伯格效应，表现为耗氧率（OCR）和ATP生成增加，糖酵解酶表达及乳酸分泌减少。同时，IGFL2通过STAT1/STAT6信号通路促进M2巨噬细胞极化，增加CD11b + CD206 + M2细胞比例并抑制M1极化。在体内，IGFL2基因敲低显著抑制异种移植模型中的肿瘤生长和代谢重编程。这些发现表明，IGFL2通过双重机制促进OC转移：调节代谢重编程（瓦伯格效应）和影响肿瘤相关巨噬细胞（TAM）极化。
