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
: Neoplasia
: 100987
: 51
: 1476-5586
: 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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