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

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

Publisher: Elsevier

: 2024

: Neoplasia

: 100987

: 51

: 1476-5586

DOI: https://doi.org/10.1016/j.neo.2024.100987

: https://doi.org/10.1016/j.neo.2024.100987

: https://research.utu.fi/converis/portal/detail/Publication/387295157

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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