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

Neoplasia. 2024 Mar 14;51:100987. doi: 10.1016/j.neo.2024.100987. Online ahead of print.ABSTRACTGene 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.PMID:38489912 | DOI:10.1016/j.neo.2024.100987

Source: Neoplasia - March 15, 2024 Category: Cancer & Oncology Authors: Heidi Rausio Alejandra Cervera Vanina D Heuser Gun West Jaana Oikkonen Elena Pianfetti Marta Lovino Elisa Ficarra Pekka Taimen Johanna Hynninen Rainer Lehtonen Sampsa Hautaniemi Olli Carp én Kaisa Huhtinen Source Type: research