Gene fusions are common in high-grade serous ovarian cancer (HGSC). Such genetic lesions may promote tumorigenesis, but the pathogenic mechanisms are currently poorly understood. Here, we investigated the role of a PIK3R1-CCDC178 fusion identified from a patient with advanced HGSC. We show that the fusion induces HGSC cell migration by regulating ERK1/2 and increases resistance to platinum treatment. Platinum resistance was associated with rod and ring-like cellular structure formation. These structures contained, in addition to the fusion protein, CIN85, a key regulator of PI3K-AKT-mTOR signaling. Our data suggest that the fusion-driven structure formation induces a previously unrecognized cell survival and resistance mechanism, which depends on ERK1/2-activation.

中文翻译：

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PIK3R1融合通过激活ERK1/2并诱导杆状和环状结构来驱动卵巢癌的化疗耐药性

基因融合在高级别浆液性卵巢癌（HGSC）中很常见。这种基因损伤可能促进肿瘤发生，但目前对其致病机制知之甚少。在这里，我们研究了从晚期 HGSC 患者身上鉴定出的 PIK3R1-CCDC178 融合蛋白的作用。我们发现融合通过调节 ERK1/2 诱导 HGSC 细胞迁移并增加对铂治疗的抵抗力。铂电阻与棒状和环状细胞结构的形成有关。除了融合蛋白之外，这些结构还包含 CIN85，它是 PI3K-AKT-mTOR 信号传导的关键调节因子。我们的数据表明，融合驱动的结构形成诱导了先前未被识别的细胞存活和抵抗机制，这取决于 ERK1/2 激活。