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

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.


Citation:

Rausio, H.; Cervera, A.; Heuser, V. D.; West, G.; Oikkonen, J.; Pianfetti, E.; Lovino, M.; Ficarra, E.; Taimen, P.; Hynninen, J.; Lehtonen, R.; Hautaniemi, S.; Carpen, O.; Huhtinen, K. "PIK3R1 fusion drives chemoresistance in ovarian cancer by activating ERK1/2 and inducing rod and ring-like structures" NEOPLASIA, vol. 51, pp. 1 -10 , 2024 DOI: 10.1016/j.neo.2024.100987

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