PT - JOURNAL ARTICLE AU - ENDO, IHIRO AU - AMATYA, VISHWA JEET AU - KUSHITANI, KEI AU - KAMBARA, TAKAHIRO AU - NAKAGIRI, TETSUYA AU - AOE, KOHEI AU - TAKESHIMA, YUKIO TI - FOXM1 Promotes Mesothelioma Cell Migration and Invasion <em>via</em> Activation of SMAD Signaling AID - 10.21873/anticanres.16583 DP - 2023 Sep 01 TA - Anticancer Research PG - 3961--3968 VI - 43 IP - 9 4099 - http://ar.iiarjournals.org/content/43/9/3961.short 4100 - http://ar.iiarjournals.org/content/43/9/3961.full SO - Anticancer Res2023 Sep 01; 43 AB - Background/Aim: 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. Materials and Methods: 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. Results: 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. Conclusion: IGF2BP3/FOXM1 promotes mesothelioma cell migration and invasion via SMAD signaling, highlighting IGF2BP3/FOXM1 as a potential target for mesothelioma treatment.