Forkhead Box M1 Is Essential for Nuclear Localization of Glioma-associated Oncogene Homolog 1 in Glioblastoma Multiforme Cells by Promoting Importin-7 Expression

Xue, Jianfei; Zhou, Aidong; Tan, Chong Oon; Wu, Yamei; Lee, Hsueh Te; Li, Wenliang; Xie, Keping; Huang, Suyun

doi:10.1074/jbc.m115.662882

Cited by 29 publications

(24 citation statements)

References 32 publications

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“…FoxM1 was shown to participate in the nuclear accumulation of b-catenin following activation of Wnt-signaling. Moreover, in glioblastoma, it promotes nuclear accumulation of GLI1, a mediator of the Hedgehog pathway, by increasing expression of Importin-720. FoxM1 has been linked also to STAT3 activation in gliobastoma21.…”

mentioning

confidence: 99%

Plk1 Regulates the Repressor Function of FoxM1b by inhibiting its Interaction with the Retinoblastoma Protein

Mukhopadhyay

Chand

Pandey

et al. 2017

Sci Rep

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FoxM1b is a cell cycle-regulated transcription factor, whose over-expression is a marker for poor outcome in cancers. Its transcriptional activation function requires phosphorylation by Cdk1 or Cdk2 that primes FoxM1b for phosphorylation by Plk1, which triggers association with the co-activator CBP. FoxM1b also possesses transcriptional repression function. It represses the mammary differentiation gene GATA3 involving DNMT3b and Rb. We investigated what determines the two distinct functions of FoxM1b: activation and repression. We show that Rb binds to the C-terminal activation domain of FoxM1b. Analyses with phospho-defective and phospho-mimetic mutants of FoxM1b identified a critical role of the Plk1 phosphorylation sites in regulating the binding of FoxM1b to Rb and DNMT3b. That is opposite of what was seen for the interaction of FoxM1b with CBP. We show that, in addition to GATA3, FoxM1b also represses the mammary luminal differentiation marker FoxA1 by promoter-methylation, and that is regulated by the Plk1 phosphorylation sites in FoxM1b. Our results show that the Plk1 phosphorylation sites in FoxM1b serve as a regulator for its repressor function, and they provide insights into how FoxM1b inhibits differentiation genes and activates proliferation genes during cancer progression.

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confidence: 99%

Plk1 Regulates the Repressor Function of FoxM1b by inhibiting its Interaction with the Retinoblastoma Protein

Mukhopadhyay

Chand

Pandey

et al. 2017

Sci Rep

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“…Second, FOXM1 is overrepresented in GBM patients and its expression levels are inversely correlated with glioma patients' survival period using the CGGA dataset [34] (Figure 5E). Last, FOXM1 stimulates self-renewal, tumorigenicity and invasiveness of glioblastoma stem-like cells by transactivating a number of molecules, including IPO7 (importing-7), CDC20 , PDGF-A , ANXA1 , MMP-2 and VEGF [37–41]. FOXM1 also promotes β-catenin nuclear localization and controls Wnt target-gene expression during glioma tumorigenesis [42].…”

Section: Resultsmentioning

confidence: 99%

HMGA2 sustains self-renewal and invasiveness of glioma-initiating cells

Zhong

Luo

et al. 2016

Oncotarget

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Glioblastoma multiforme (GBM) is the most common type of brain tumors with dismal outcomes. The mesenchymal phenotype is the hallmark of tumor aggressiveness in GBMs. Perivascular smooth muscle cells (pericytes) are essential in homeostasis of normal and glioma tissues. Here we found HMGA2, an architectural transcription factor that promotes mesenchymal phenotypes in a number of solid tumors, is highly expressed in mesenchymal subtype of GBMs and labels both glioma pericytes and glioma-initiating cells (GICs). Accordingly, depletion of HMGA2 in GICs resulted in compromised self-renewal and tumorigenic capability, as well as undermined mesenchymal or pericyte differentiation. We further showed HMGA2 allows expressions of FOXM1 and PLAU to maintain GIC propagation, gliomagenesis and aggressiveness both in vitro and in vivo. Therefore, suppressing HMGA2-mediated GIC self-renewal and invasiveness might be a promising means to treat GBMs.

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“…Considerable efforts have been exerted in recent years to elucidate the translation and activity of FOXM1 (46). The Hh signaling pathway may modulate the transcription of FOXM1 in human transitional cell carcinoma of the bladder (47).…”

Section: A B C D E F G Hmentioning

confidence: 99%

Association between FOXM1 and hedgehog signaling pathway in human cervical carcinoma by tissue microarray analysis

et al. 2016

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Abstract. Forkhead box M1 (FOXM1) and hedgehog (Hh) signaling pathway are implicated in the formation and development of human tumors, including cervical cancer. Previous studies have indicated that FOXM1 may be a downstream target gene of the Hh signaling pathway, but their association in cervical cancer is largely unknown. In the present study, the expression of FOXM1 and Hh signaling molecules was evaluated by immunohistochemical analysis in a tissue microarray that contained 70 cervical cancer tissues and 10 normal cervical tissues. In addition, the association of these molecules with clinicopathological parameters, and the association between FOXM1 and various molecules involved in the Hh signaling pathway was investigated. The results indicated that FOXM1 and Hh signaling molecules were overexpressed in cervical cancer tissues. The protein expression levels of FOXM1, glioma-associated oncogene 1 (GLI1) and smoothened (SMO) correlated with the clinical stage of the tumors, while the protein expression levels of Sonic Hh (SHh), patched 1 (PTCH1) and GLI1 correlated with the pathological grade of the tumors. The expression levels of GLI1 were lower in tissues without lymph node metastasis than in tissues with lymph node metastasis. In addition, FOXM1 expression correlated with GLI1, SHh and PTCH1 expression in cancer tissues. These findings confirmed the participation of FOXM1 and the Hh signaling pathway in cervical cancer. Furthermore, the finding that FOXM1 may be a downstream target gene of the Hh signaling pathway in cervical cancer provides a potential novel diagnostic and therapeutic target for cervical cancer.

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Forkhead Box M1 Is Essential for Nuclear Localization of Glioma-associated Oncogene Homolog 1 in Glioblastoma Multiforme Cells by Promoting Importin-7 Expression

Cited by 29 publications

References 32 publications

Plk1 Regulates the Repressor Function of FoxM1b by inhibiting its Interaction with the Retinoblastoma Protein

Plk1 Regulates the Repressor Function of FoxM1b by inhibiting its Interaction with the Retinoblastoma Protein

HMGA2 sustains self-renewal and invasiveness of glioma-initiating cells

Association between FOXM1 and hedgehog signaling pathway in human cervical carcinoma by tissue microarray analysis

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