PIK3R1 fusion drives chemoresistance in ovarian cancer by activating ERK1/2 and inducing rod and ring-like structures

IF 4.8 2区医学 Q1 Biochemistry, Genetics and Molecular Biology

Neoplasia Pub Date : 2024-03-14 DOI:10.1016/j.neo.2024.100987

Heidi Rausio , Alejandra Cervera , Vanina D. Heuser , Gun West , Jaana Oikkonen , Elena Pianfetti , Marta Lovino , Elisa Ficarra , Pekka Taimen , Johanna Hynninen , Rainer Lehtonen , Sampsa Hautaniemi , Olli Carpén , Kaisa Huhtinen

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引用次数: 0

Abstract

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.

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PIK3R1融合通过激活ERK1/2和诱导棒状和环状结构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。这种基因病变可能会促进肿瘤发生，但目前对其致病机制还知之甚少。在这里，我们研究了从一名晚期 HGSC 患者身上发现的 PIK3R1-CCDC178 融合基因的作用。我们发现，该融合体通过调节ERK1/2诱导HGSC细胞迁移，并增加对铂治疗的耐药性。铂金抗性与杆状和环状细胞结构的形成有关。这些结构中除了融合蛋白外，还含有PI3K-AKT-mTOR信号转导的关键调节因子CIN85。我们的数据表明，融合驱动的结构形成诱导了一种之前尚未认识到的细胞存活和抗性机制，这种机制依赖于ERK1/2的激活。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neoplasia 医学-肿瘤学

CiteScore

9.20

自引率

2.10%

发文量

审稿时长

26 days

期刊介绍： Neoplasia publishes the results of novel investigations in all areas of oncology research. The title Neoplasia was chosen to convey the journal’s breadth, which encompasses the traditional disciplines of cancer research as well as emerging fields and interdisciplinary investigations. Neoplasia is interested in studies describing new molecular and genetic findings relating to the neoplastic phenotype and in laboratory and clinical studies demonstrating creative applications of advances in the basic sciences to risk assessment, prognostic indications, detection, diagnosis, and treatment. In addition to regular Research Reports, Neoplasia also publishes Reviews and Meeting Reports. Neoplasia is committed to ensuring a thorough, fair, and rapid review and publication schedule to further its mission of serving both the scientific and clinical communities by disseminating important data and ideas in cancer research.