Forkhead box M1 (FOXM1) gene expression inversely correlates with survival and targeting FOXM1 improves cytotoxicity of paclitaxel and cisplatinum in platinum-resistant ovarian cancer ascites cells ex vivo

2014 ◽  
Vol 133 ◽  
pp. 90 ◽  
Author(s):  
G.L. Westhoff ◽  
Y. Chen ◽  
M. Bieber ◽  
N.N.H. Teng
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Ex Vivo ◽  
Forkhead Box ◽  
Platinum Resistant ◽  
Forkhead Box M1

scholarly journals The forkhead box L2 transcription factor (FOXL2) is differentially expressed in high-grade serous ovarian cancers.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Expression Profiles ◽  
Gynecologic Cancer ◽  
Ovarian Tumors ◽  
High Grade ◽  
Normal Ovary ◽  
Primary Tumors ◽  
Forkhead Box ◽  
Ovarian Cancers

Ovarian cancer is the most lethal gynecologic cancer (1). We sought to identify genes associated with high-grade serous ovarian cancer (HGSC) by comparing global gene expression profiles of normal ovary with that of primary tumors from women diagnosed with HGSC using published microarray data (2, 3). We identified the forkhead box L2, (FOXL2) (4) as among the genes whose expression was most different in HGSC ovarian tumors. FOXL2 expression was significantly lower in ovarian tumors relative to normal ovary. FOXL2 has established roles in ovarian development (4, 5), and the FOXL2 gene is mutated in granulosa-cell tumors of the ovary (6). These data indicate FOXL2 might also be perturbed, at the level of gene expression, in high-grade serous ovarian cancers.

scholarly journals FOXM1: A Multifunctional Oncoprotein and Emerging Therapeutic Target in Ovarian Cancer

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3065
Author(s):  
Cassie Liu ◽  
Carter J. Barger ◽  
Adam R. Karpf
Keyword(s):  
Ovarian Cancer ◽  
Therapeutic Target ◽  
Current Knowledge ◽  
Chemotherapy Resistance ◽  
Invasion And Metastasis ◽  
Transcriptional Signature ◽  
Forkhead Box ◽  
Forkhead Box M1 ◽  
Foxm1 Expression ◽  
Translational Mechanisms

Forkhead box M1 (FOXM1) is a member of the conserved forkhead box (FOX) transcription factor family. Over the last two decades, FOXM1 has emerged as a multifunctional oncoprotein and a robust biomarker of poor prognosis in many human malignancies. In this review article, we address the current knowledge regarding the mechanisms of regulation and oncogenic functions of FOXM1, particularly in the context of ovarian cancer. FOXM1 and its associated oncogenic transcriptional signature are enriched in >85% of ovarian cancer cases and FOXM1 expression and activity can be enhanced by a plethora of genomic, transcriptional, post-transcriptional, and post-translational mechanisms. As a master transcriptional regulator, FOXM1 promotes critical oncogenic phenotypes in ovarian cancer, including: (1) cell proliferation, (2) invasion and metastasis, (3) chemotherapy resistance, (4) cancer stem cell (CSC) properties, (5) genomic instability, and (6) altered cellular metabolism. We additionally discuss the evidence for FOXM1 as a cancer biomarker, describe the rationale for FOXM1 as a cancer therapeutic target, and provide an overview of therapeutic strategies used to target FOXM1 for cancer treatment.

scholarly journals Differential expression of forkhead box M1 in human epithelial ovarian cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Fallopian Tube ◽  
Expression Profiles ◽  
High Grade ◽  
Primary Tumors ◽  
Forkhead Box ◽  
Ovarian Cancers ◽  
Forkhead Box M1 ◽  
Foxm1 Expression

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We performed discovery of genes associated with epithelial ovarian cancer and of the high-grade serous ovarian cancer (HGSC) subtype, using published microarray data (2, 3) to compare global gene expression profiles of normal ovary or fallopian tube with that of primary tumors from women diagnosed with epithelial ovarian cancer or HGSC. We identified the gene encoding forkhead box M1, FOXM1, as among the genes whose expression was most different in epithelial ovarian cancer as compared to the normal fallopian tube. FOXM1 expression was significantly higher in high-grade serous ovarian tumors relative to normal fallopian tube. FOXM1 expression correlated with progression-free survival in patients with ovarian cancer. These data indicate that expression of FOXM1 is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. FOXM1 may be relevant to pathways underlying ovarian cancer initiation (transformation) or progression.

An Integrated Genomic-Based Approach to Individualized Treatment of Patients With Advanced-Stage Ovarian Cancer

2007 ◽  
Vol 25 (5) ◽  
pp. 517-525 ◽  
Author(s):  
Holly K. Dressman ◽  
Andrew Berchuck ◽  
Gina Chan ◽  
Jun Zhai ◽  
Andrea Bild ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Advanced Stage ◽  
Platinum Resistant ◽  
Ovarian Cancer Cell Lines ◽  
Platinum Based Chemotherapy

Purpose The purpose of this study was to develop an integrated genomic-based approach to personalized treatment of patients with advanced-stage ovarian cancer. We have used gene expression profiles to identify patients likely to be resistant to primary platinum-based chemotherapy and also to identify alternate targeted therapeutic options for patients with de novo platinum-resistant disease. Patients and Methods A gene expression model that predicts response to platinum-based therapy was developed using a training set of 83 advanced-stage serous ovarian cancers and tested on a 36-sample external validation set. In parallel, expression signatures that define the status of oncogenic signaling pathways were evaluated in 119 primary ovarian cancers and 12 ovarian cancer cell lines. In an effort to increase chemotherapy sensitivity, pathways shown to be activated in platinum-resistant cancers were subject to targeted therapy in ovarian cancer cell lines. Results Gene expression profiles identified patients with ovarian cancer likely to be resistant to primary platinum-based chemotherapy with greater than 80% accuracy. In patients with platinum-resistant disease, we identified expression signatures consistent with activation of Src and Rb/E2F pathways, components of which were successfully targeted to increase response in ovarian cancer cell lines. Conclusion We have defined a strategy for treatment of patients with advanced-stage ovarian cancer that uses therapeutic stratification based on predictions of response to chemotherapy, coupled with prediction of oncogenic pathway deregulation, as a method to direct the use of targeted agents.

scholarly journals Rosmarinic Acid Methyl Ester Regulates Ovarian Cancer Cell Migration and Reverses Cisplatin Resistance by Inhibiting the Expression of Forkhead Box M1

2020 ◽  
Vol 13 (10) ◽  
pp. 302
Author(s):  
Soo Hyun Lim ◽  
Ki Hong Nam ◽  
Kyungtae Kim ◽  
Sang Ah Yi ◽  
Jaecheol Lee ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Methyl Ester ◽  
Cancer Cells ◽  
Rosmarinic Acid ◽  
Target Genes ◽  
Acid Methyl Ester ◽  
Ovarian Cancer Cells ◽  
Forkhead Box ◽  
Acid Methyl ◽  
Forkhead Box M1

Rosmarinic acid methyl ester (RAME), a derivative of rosmarinic acid (RA), is reported to have several therapeutic effects, including anti-tumor effects against cervical cancer. However, its anti-tumor effects in ovarian cancer is unclear. In this study, we studied the molecular pathways associated with the anti-tumor effects of RAME in ovarian cancer. To identify the effects of RAME in ovarian cancer, RNA sequencing was performed in RAME-treated ovarian cancer cells; we found that RAME treatment downregulated the genes closely involved with the target genes of the transcription factor Forkhead box M1 (FOXM1). It was reported that FOXM1 is overexpressed in a variety of cancer cells and is associated with cell proliferation and tumorigenesis. Therefore, we hypothesized that FOXM1 is a key target of RAME; this could result in its anti-tumor effects. Treatment of ovarian cancer cells with RAME-inhibited cell migration and invasion, as shown by wound healing and transwell migration assays. To examine whether RAME represses the action of FOXM1, we performed quantitative RT-PCR and ChIP-qPCR. Treatment of ovarian cancer cells with RAME decreased the mRNA expression of FOXM1 target genes and the binding of FOXM1 to its target genes. Moreover, FOXM1 expression was increased in cisplatin-resistant ovarian cancer cells, and combination treatment with RAME and cisplatin sensitized the cisplatin-resistant ovarian cancer cells, which was likely due to FOXM1 inhibition. Our research suggests that RAME is a promising option in treating ovarian cancer patients, as it revealed a novel molecular pathway underlying its anti-tumor effects.

A molecular signature for identification of platinum resistant ovarian cancer

2008 ◽  
Vol 68 (S 01) ◽  
Author(s):  
T Fehm ◽  
M Bonin ◽  
J Hoffmann ◽  
K Sotlar ◽  
E Solomayer ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Molecular Signature ◽  
Platinum Resistant
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