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.

PIK3R1 fusion drives chemoresistance in ovarian cancer by activating ERK1/2 and inducing rod and ring-like structures / 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.. - In: NEOPLASIA. - ISSN 1522-8002. - 51:(2024), pp. 1-10. [10.1016/j.neo.2024.100987]

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

Pianfetti E.;Lovino M.;Ficarra E.;
2024

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.
2024
51
1
10
PIK3R1 fusion drives chemoresistance in ovarian cancer by activating ERK1/2 and inducing rod and ring-like structures / 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.. - In: NEOPLASIA. - ISSN 1522-8002. - 51:(2024), pp. 1-10. [10.1016/j.neo.2024.100987]
Rausio, H.; Cervera, A.; Heuser, V. D.; West, G.; Oikkonen, J.; Pianfetti, E.; Lovino, M.; Ficarra, E.; Taimen, P.; Hynninen, J.; Lehtonen, R.; Hautan...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1342048
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