Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
Filamin C activates MAPK/ERK signaling to facilitate epithelial-mesenchymal transition in bladder cancer.
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Li Chen, Yang Zhichao, Zhang Jialei, Yan Xiaodong, Su Hongwei
Аннотация
BACKGROUND: Bladder cancer (BC) is a prevalent malignancy with high metastatic and recurrent potential. Filamin C (FLNC) has been reported implicated in various cancers, but its role in BC remains unclear.
METHODS: Bioinformatics analysis using The gene expression profiling interactive analysis (GEPIA) and The cancer genome atlas (TCGA) databases assessed FLNC expression, prognosis, and multivariate Cox regression in bladder urothelial carcinoma (BLCA). Human protein atlas (HPA) database provided immunohistochemical images. In vitro, CCK-8, wound healing, Transwell, and western blotting (WB) assays evaluated BC cell proliferation, migration, invasion, epithelial‑mesenchymal transition (EMT), and MAPK/ERK signaling. Co‑immunoprecipitation and immunofluorescence examined FLNC‑MEK1/2 interaction and co‑localization. Rescue experiments used the MEK agonist C16‑PAF or inhibitor U0126. In vivo, the effects of FLNC on BC progression and lung metastasis were verified through nude mouse xenograft tumor models and lung metastasis models, with WB and immunohistochemistry detecting EMT and MAPK/ERK pathway proteins.
RESULTS: FLNC was upregulated in different disease stages of BLCA and was associated with poor prognosis. In vitro, FLNC significantly promoted the proliferation, migration, and invasion abilities of BC cells and facilitated the EMT process. In vivo, FLNC promoted tumor growth, lung metastasis, and EMT. Mechanistically, FLNC directly interacted with MEK1/2 and co‑localized in the cytoplasm, activating the MAPK/ERK pathway. Rescue experiments showed that a MEK agonist reversed the effects of FLNC knockdown, while a MEK inhibitor reversed the effects of FLNC overexpression.
CONCLUSION: FLNC drives BC progression and metastasis via MAPK/ERK activation and EMT induction.
METHODS: Bioinformatics analysis using The gene expression profiling interactive analysis (GEPIA) and The cancer genome atlas (TCGA) databases assessed FLNC expression, prognosis, and multivariate Cox regression in bladder urothelial carcinoma (BLCA). Human protein atlas (HPA) database provided immunohistochemical images. In vitro, CCK-8, wound healing, Transwell, and western blotting (WB) assays evaluated BC cell proliferation, migration, invasion, epithelial‑mesenchymal transition (EMT), and MAPK/ERK signaling. Co‑immunoprecipitation and immunofluorescence examined FLNC‑MEK1/2 interaction and co‑localization. Rescue experiments used the MEK agonist C16‑PAF or inhibitor U0126. In vivo, the effects of FLNC on BC progression and lung metastasis were verified through nude mouse xenograft tumor models and lung metastasis models, with WB and immunohistochemistry detecting EMT and MAPK/ERK pathway proteins.
RESULTS: FLNC was upregulated in different disease stages of BLCA and was associated with poor prognosis. In vitro, FLNC significantly promoted the proliferation, migration, and invasion abilities of BC cells and facilitated the EMT process. In vivo, FLNC promoted tumor growth, lung metastasis, and EMT. Mechanistically, FLNC directly interacted with MEK1/2 and co‑localized in the cytoplasm, activating the MAPK/ERK pathway. Rescue experiments showed that a MEK agonist reversed the effects of FLNC knockdown, while a MEK inhibitor reversed the effects of FLNC overexpression.
CONCLUSION: FLNC drives BC progression and metastasis via MAPK/ERK activation and EMT induction.