Down-regulation of Forkhead Box M1 Transcription Factor Leads to the Inhibition of Invasion and Angiogenesis of Pancreatic Cancer Cells

Wang, Zhiwei; Banerjee, Sanjeev; Kong, Dejuan; Li, Yiwei; Sarkar, Fazlul H.

doi:10.1158/0008-5472.can-07-1265

Cited by 238 publications

(234 citation statements)

References 37 publications

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“…Recent studies including genomewide expression profiles have demonstrated that FoxM1 signaling network is disturbed and highly expressed in many human malignancies [15][16][17][18][19][20]. The present study also showed that FoxM1 mRNA is highly expressed in T-cell ALL line and inhibition of this transcription factor resulted in a profound decrease in leukemic cell proliferation.…”

Section: Discussionsupporting

confidence: 73%

“…Furthermore, depletion of FoxM1 has been shown to cause mitotic spindle defects, cell cycle arrest, chromosome misaggregation and mitotic catastrophe [12,13]. Recent reports have also demonstrated that FoxM1 plays important roles in cellular developmental pathways including the maintenance of homeostasis between cell proliferation and apoptosis and as a result, alterations in FoxM1 signaling has been reported to be associated with carcinogenesis and tumor aggressiveness [8,9,14] cancer, glioblastomas, prostate cancer, basal cell carcinomas and pancreas cancer [15][16][17][18][19]. These results give rise to some questions about the role of FoxM1 in pathogenesis of leukemia.…”

Section: Introductionmentioning

confidence: 99%

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Targeting FoxM1 transcription factor in T-cell acute lymphoblastic leukemia cell line

et al. 2015

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The Forkhead box protein M1 (FoxM1) is an important transcription factor having significant roles in various cellular events. FoxM1 overexpression has been reported to be related with many types of cancer. However, it is not known whether it contributes to oncogenesis of acute lymphoblastic leukemia. Siomycin A, a thiazol antibiotic, is known to inhibit FoxM1 transcriptional activity. In this study, we aimed to determine gene expression levels of FoxM1 in Jurkat cells (T-cell acute lymphoblastic leukemia cell line) and therapeutic potential of targeting FoxM1 by siomycin A alone and in combination with dexamethasone which improves the survival of children with T-cell acute lymphoblastic leukemia (ALL). We also examined the molecular mechanisms of siomycin A and dexamethasone-induced cell death in Jurkat cells. We demonstrated that FoxM1 mRNA is highly expressed in Jurkat cells. Dexamethasone and siomycin A caused a significant reduction in gene expression levels of FoxM1 in Jurkat cells. Targeting FoxM1 by siomycin A and dexamethasone caused a significant decrease in T-ALL cell line proliferation through induction of G1 cell cycle arrest. All these findings suggest a possible role of FoxM1 in T-cell ALL pathogenesis and represent FoxM1 as an attractive target for T-cell ALL therapy. © 2014 Elsevier Ltd.Dokuz Eylul University Scientific Research Projects Coordination Unit (99.3456.23

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Section: Discussionsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Targeting FoxM1 transcription factor in T-cell acute lymphoblastic leukemia cell line

et al. 2015

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“…Besides cell proliferation, FOXM1 is also needed for cell migration and transformation (10,12), and as such, we reasoned that thiostrepton should repress cell migration and transformation in breast cancer cells through the down-regulation of FOXM1 expression. To test this hypothesis, we did wound-healing assays on MCF-7 breast cancer cells in the presence of 0, 10, and 20 Amol/L thiostrepton (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…An increase in FOXM1 activity may promote tumorigenesis through driving proliferation and cell cycle by regulating downstream targets such as cyclin B1 (9), Skp2-Csk1 ubiquitin ligase complex (10), CDC25b phosphatase, and Polo-like kinase-1 (11). Moreover, FOXM1 can also activate other genes involved in metastasis and angiogenesis such as the matrix metalloproteinase (MMP)-2, MMP-9, and vascular endothelial growth factor (12).…”

Section: Introductionmentioning

confidence: 99%

“…Remarkably, loss of the foxm1 gene in hepatocytes of 6-week-old transgenic mice resulted in resistance to the induction of hepatocellular carcinoma following exposure to carcinogens (14). In pancreatic cell lines, small interfering RNA knockdown of FOXM1 expression lead to a decrease level of MMP-9, MMP-2, and vascular endothelial growth factor, thereby decreasing metastasis and angiogenesis respectively (12).…”

Section: Introductionmentioning

confidence: 99%

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Thiostrepton selectively targets breast cancer cells through inhibition of forkhead box M1 expression

Kwok

Myatt

Marson

et al. 2008

Molecular Cancer Therapeutics

215

200

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Elevated expression or activity of the transcription factor forkhead box M1 (FOXM1) is associated with the development and progression of many malignancies, including breast cancer. In this study, we show that the thiazole antibiotic thiostrepton selectively induces cell cycle arrest and cell death in breast cancer cells through down-regulating FOXM1 expression. Crucially, our data show that thiostrepton treatment reduced FOXM1 expression in a time-and dose-dependent manner, independent of de novo protein synthesis and predominantly at transcriptional and gene promoter levels. Our results indicate that thiostrepton can induce cell death through caspase-dependent intrinsic and extrinsic apoptotic pathways as well as through caspase-independent death mechanisms, as observed in MCF-7 cells, which are deficient of caspase-3 and caspase-7. Cell cycle analysis showed that thiostrepton induced cell cycle arrest at G 1 and S phases and cell death, concomitant with FOXM1 repression in breast cancer cells. Furthermore, thiostrepton also shows efficacy in repressing breast cancer cell migration, metastasis, and transformation, which are all downstream functional attributes of FOXM1. We also show that overexpression of a constitutively active FOXM1 mutant, #N-FOXM1, can abrogate the antiproliferative effects of thiostrepton. Interestingly, thiostrepton has no affect on FOXM1 expression and proliferation of the untransformed MCF-10A breast epithelial cells. Collectively, our data show that FOXM1 is one of the primary cellular targets of thiostrepton in breast cancer cells and that thiostrepton may represent a novel lead compound for targeted therapy of breast cancer with minimal toxicity against noncancer cells.

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Hypoxia‐driven paracrine osteopontin/integrin αvβ3 signaling promotes pancreatic cancer cell epithelial–mesenchymal transition and cancer stem cell‐like properties by modulating forkhead box protein M1

Cao

Sun

et al. 2018

Molecular Oncology

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Pancreatic stellate cells (PSCs), a key component of the tumor microenvironment, contribute to tumor invasion, metastasis, and chemoresistance. Osteopontin (OPN), a phosphorylated glycoprotein, is overexpressed in pancreatic cancer. However, OPN expression in PSCs and its potential roles in tumor–stroma interactions remain unclear. The present study first showed that OPN is highly expressed and secreted in activated PSCs driven by hypoxia, and this process is in a ROS‐dependent manner; in addition, OPN was shown to be involved in the PSC‐induced epithelial–mesenchymal transition (EMT) and cancer stem cell (CSC)‐like properties of pancreatic cancer cells (PCCs). Mechanistically, OPN from activated PSCs interacts with the transmembrane receptor integrin αvβ3 on PCCs to upregulate forkhead box protein M1 (FOXM1) expression and induce malignant phenotypes of PCCs. Moreover, the Akt and Erk pathways participate in OPN/integrin αvβ3 axis‐induced FOXM1 expression of PCCs. Our further analysis showed that OPN and FOXM1 are significantly upregulated in pancreatic cancer tissues and are associated with poor clinical outcome, indicating that OPN and FOXM1 might be considered as diagnostic and prognostic biomarkers for patients with pancreatic cancer. In conclusion, we show here for the first time that OPN promotes the EMT and CSC‐like properties of PCCs by activating the integrin αvβ3‐Akt/Erk‐FOXM1 cascade in a paracrine manner, suggesting that targeting the tumor microenvironment represents a promising therapeutic strategy in pancreatic cancer.

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Down-regulation of Forkhead Box M1 Transcription Factor Leads to the Inhibition of Invasion and Angiogenesis of Pancreatic Cancer Cells

Cited by 238 publications

References 37 publications

Targeting FoxM1 transcription factor in T-cell acute lymphoblastic leukemia cell line

Targeting FoxM1 transcription factor in T-cell acute lymphoblastic leukemia cell line

Thiostrepton selectively targets breast cancer cells through inhibition of forkhead box M1 expression

Hypoxia‐driven paracrine osteopontin/integrin αvβ3 signaling promotes pancreatic cancer cell epithelial–mesenchymal transition and cancer stem cell‐like properties by modulating forkhead box protein M1

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