IGF2BP1 is a targetable SRC/MAPK-dependent driver of invasive growth in ovarian cancer

We identified IGF2BP1 as a marker of the C5 molecular subtype of high-grade ovarian carcinoma (HG-SOC). IGF2BP1 promotes SRC activity and ERK2 expression enhancing the tolerance towards SRC- and MEK-directed inhibitors saracatinib and selumetib. Combination treatment overcomes IGF2BP1-promoted resistance. PolyA-RNA sequencing of tumor samples was performed to investigate correlation of IGF2BP1 to molecular signatures and identify the molecular subtypes of the respective tumor samples.

本研究鉴定出胰岛素样生长因子2 mRNA结合蛋白1（IGF2BP1）可作为高级别浆液性卵巢癌（HG-SOC）C5分子亚型的标志物。IGF2BP1可增强Src激酶（SRC）活性与细胞外调节蛋白激酶2（ERK2）的表达，进而提升肿瘤细胞对Src靶向抑制剂萨拉替尼（saracatinib）与MEK靶向抑制剂司美替尼（selumetib）的耐受性。联合用药可逆转IGF2BP1介导的耐药性。本研究对肿瘤样本开展PolyA-RNA测序，以探究IGF2BP1与分子特征的关联，并鉴定对应肿瘤样本的分子亚型。