FOXM1 Promotes Mesothelioma Cell Migration and Invasion via Activation of SMAD Signaling.

Ihiro Endo, Vishwa Jeet Amatya, Kei Kushitani, Takahiro Kambara, Tetsuya Nakagiri, Kohei Aoe, Yukio Takeshima

Anticancer research 2023 Sep

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Forkhead box M1 (FOXM1) is a transcription factor closely associated with various human malignancies and is considered an attractive target for cancer therapy. Mesothelioma is a malignancy primarily due to asbestos exposure and certain genetic factors, requiring a better understanding of tumorigenesis for improved treatment. Asbestos-exposed human mesothelial cells have been reported to up-regulate FOXM1 expression in a dose-dependent manner. FOXM1 expression was evaluated in mesothelioma tissues and cell lines. FOXM1 small interfering RNA was transfected into mesothelioma cell lines to analyze its biological functions and regulatory mechanisms. FOXM1 was over-expressed in mesothelioma tissues and cell lines. Knock-down of FOXM1 in mesothelioma cell lines inhibited cell proliferation, migration, and invasion. These results suggest that up-regulation of FOXM1 expression promotes mesothelioma tumorigenesis and progression. We previously reported that insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) promotes the proliferation, migration, and invasion of mesothelioma cell lines. In this study, IGF2BP3 knock-down suppressed FOXM1 expression in mesothelioma cell lines. Our results suggest that IGF2BP3, an upstream regulator, contributes to increased FOXM1 expression. Furthermore, IGF2BP3 and FOXM1 knock-down suppressed SMAD signaling by inhibiting SMAD2/3 phosphorylation in mesothelioma cell lines. IGF2BP3/FOXM1 promotes mesothelioma cell migration and invasion via SMAD signaling, highlighting IGF2BP3/FOXM1 as a potential target for mesothelioma treatment. Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Citation

Ihiro Endo, Vishwa Jeet Amatya, Kei Kushitani, Takahiro Kambara, Tetsuya Nakagiri, Kohei Aoe, Yukio Takeshima. FOXM1 Promotes Mesothelioma Cell Migration and Invasion via Activation of SMAD Signaling. Anticancer research. 2023 Sep;43(9):3961-3968