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

被引：1

作者：

Rausio, Heidi ^{[1
,2
,3
]}

Cervera, Alejandra ^{[4
,5
]}

Heuser, Vanina D. ^{[1
,2
]}

West, Gun ^{[1
,2
]}

Oikkonen, Jaana ^{[4
]}

Pianfetti, Elena ^{[6
]}

Lovino, Marta ^{[6
]}

Ficarra, Elisa ^{[6
]}

Taimen, Pekka ^{[1
,2
,7
]}

Hynninen, Johanna ^{[8
,9
]}

Lehtonen, Rainer ^{[4
]}

Hautaniemi, Sampsa ^{[4
]}

Carpen, Olli ^{[4
,10
,11
]}

Huhtinen, Kaisa ^{[1
,2
,4
]}

机构：

[1] Univ Turku, Inst Biomed, Fac Med, Turku, Finland

[2] Univ Turku, Fac Med, FICAN West Canc Ctr, Turku, Finland

[3] Univ Turku, Drug Res Doctoral Programme DRDP, Turku, Finland

[4] Univ Helsinki, Fac Med, Res Program Syst Oncol, Res Programs Unit, Helsinki, Finland

[5] Inst Nacl Med Genom, Genom Computac, Mexico City, Mexico

[6] Univ Modena & Reggio Emilia, Dept Engn Enzo Ferrari, Modena, Italy

[7] Turku Univ Hosp, Dept Pathol, Turku, Finland

[8] Turku Univ Hosp, Dept Obstet & Gynecol, Turku, Finland

[9] Univ Turku, Turku, Finland

[10] Univ Helsinki, Dept Pathol, Helsinki, Finland

[11] HUSLAB, Univ Hosp, Helsinki, Finland

来源：

NEOPLASIA | 2024年 / 51卷

基金：

欧盟地平线“2020”;

关键词：

High-grade serous ovarian cancer; Fusion gene; Rods and rings (RRs); Platinum resistance; CBL-INTERACTING PROTEIN; ADAPTER PROTEIN; GENE FUSIONS; MUTATIONS; MECHANISM; 3-KINASE; PATHWAY; KINASE; CIN85;

D O I：

10.1016/j.neo.2024.100987

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：10

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