RT Journal Article
SR Electronic
T1 FOXM1 Promotes Mesothelioma Cell Migration and Invasion <em>via</em> Activation of SMAD Signaling
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 3961
OP 3968
DO 10.21873/anticanres.16583
VO 43
IS 9
A1 ENDO, IHIRO
A1 AMATYA, VISHWA JEET
A1 KUSHITANI, KEI
A1 KAMBARA, TAKAHIRO
A1 NAKAGIRI, TETSUYA
A1 AOE, KOHEI
A1 TAKESHIMA, YUKIO
YR 2023
UL http://ar.iiarjournals.org/content/43/9/3961.abstract
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.