FoxM1 promotes the migration of ovarian cancer cell through KRT5 and KRT7

Zhang, Ziyu; Tu, Kaijia; Liu, Faying; Liang, Meirong; Yu, Kaihui; Wang, Yaoqing; Luo, Yong; Yang, Bicheng; Qin, Yulin; He, Da; Jiang, Guoyi; Huang, Ouping; Zou, Yang

doi:10.1016/j.gene.2020.144947

Cited by 38 publications

(36 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…17 Although the direct links between KRT7 and the PC cell behaviors have been rarely studied, KRT7 has been widely reported to enhance growth and development of several cancers upon activation. 16,[34][35][36] In the present study, the subsequent rescue experiments suggested that overexpression of WT1 blocked the anti-tumor functions of miR-216a in PC cells; while silencing of KRT7 suppressed the oncogenic effects of WT1. In addition, either miR-216a upregulation or KRT7 silencing was found to suppress the phosphorylation of PI3K and AKT in PC cells, while WT1, as expected, activated the PI3K/ AKT signaling pathway, indicating that miR-216a mediates the WT1/KRT7 axis and impairs the PI3K/AKT pathway to suppress PC progression.…”

Section: Discussionsupporting

confidence: 55%

“…Likewise, stable high expression of KRT7 has been found in the clinical PC samples compared to the pseudotumoural chronic pancreatitis 17 . Although the direct links between KRT7 and the PC cell behaviors have been rarely studied, KRT7 has been widely reported to enhance growth and development of several cancers upon activation 16,34–36 . In the present study, the subsequent rescue experiments suggested that overexpression of WT1 blocked the anti‐tumor functions of miR‐216a in PC cells; while silencing of KRT7 suppressed the oncogenic effects of WT1.…”

Section: Discussionsupporting

confidence: 50%

See 1 more Smart Citation

MicroRNA‐216a targets WT1 expression and regulates KRT7 transcription to mediate the progression of pancreatic cancer—A transcriptome analysis

Wang

Yang

et al. 2021

IUBMB Life

View full text Add to dashboard Cite

Gene expression profiling has been broadly performed in the field of cancer research. This study aims to explore the key gene regulatory network and focuses on the functions of microRNA (miR)-216a in pancreatic cancer (PC).PC datasets GSE15471, GSE16515, and GSE32676 were used to screen the differentially expressed genes (DEGs) in PC. A miRNA microarray analysis and gene oncology analysis suggested miR-216a as an important differentially expressed miRNA in PC. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that miR-216a and the DEGs are largely enriched on the phosphatidyl inositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway. miR-216a targeted Wilms Tumor 1 (WT1), while WT1 promoted transcription activity of keratin 7 (KRT7). Upregulation of miR-216a reduced proliferation and invasiveness of PC cells, while further upregulation of WT1 blocked the functions of miR-216a. Silencing of KRT7 diminished the oncogenic role of WT1. The in vitro results were reproduced in vivo. High expression of miR-216a while poor expression of WT1 indicated better prognosis of PC patients. The miR-216a/WT1/KRT7 axis influenced the activity of the PI3K/AKT pathway. To conclude, this study evidenced that miR-216a suppressed WT1 expression and blocked KRT7 transcription, which inactivated the PI3K/AKT signaling and reduced PC progression.

show abstract

Section: Discussionsupporting

confidence: 55%

Section: Discussionsupporting

confidence: 50%

MicroRNA‐216a targets WT1 expression and regulates KRT7 transcription to mediate the progression of pancreatic cancer—A transcriptome analysis

Wang

Yang

et al. 2021

IUBMB Life

View full text Add to dashboard Cite

show abstract

“…KRT7 regulation may be in part related to Forkhead box family members. In ovarian cancer cell line SKOV3, KRT5 and KRT7 were upregulated by Forkhead box M1 (FOXM1) and KRT5 and KRT7 deficiency prevented migration [ 24 ]. FOXM1 has been widely involved in cancer progression and several molecules targeting FOXM1 pathway are currently under investigation [ 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

“…KRT7, KRT18, KRT19 protein expression in tumors were reported to predict prognosis in several cancer types [ 18 , 19 , 20 , 21 , 22 ]. However, despite reported functions of KRTs in tumor progression, relatively little is known about their value as prognostic markers in the context of HGSC [ 17 , 23 , 24 , 25 ]. Interestingly, we previously showed that KRT7 and KRT19 mRNA were elevated in OC compared to borderline tumors [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

A Keratin 7 and E-Cadherin Signature Is Highly Predictive of Tubo-Ovarian High-Grade Serous Carcinoma Prognosis

Communal

Roy

Cahuzac

et al. 2021

IJMS

View full text Add to dashboard Cite

During tubo-ovarian high-grade serous carcinoma (HGSC) progression, tumoral cells undergo phenotypic changes in their epithelial marker profiles, which are essential for dissemination processes. Here, we set out to determine whether standard epithelial markers can predict HGSC patient prognosis. Levels of E-CADH, KRT7, KRT18, KRT19 were quantified in 18 HGSC cell lines by Western blot and in a Discovery cohort tissue microarray (TMA) (n = 101 patients) using immunofluorescence. E-CADH and KRT7 levels were subsequently analyzed in the TMA of the Canadian Ovarian Experimental Unified Resource cohort (COEUR, n = 1158 patients) and in public datasets. Epithelial marker expression was highly variable in HGSC cell lines and tissues. In the Discovery cohort, high levels of KRT7 and KRT19 were associated with an unfavorable prognosis, whereas high E-CADH expression indicated a better outcome. Expression of KRT7 and E-CADH gave a robust combination to predict overall survival (OS, p = 0.004) and progression free survival (PFS, p = 5.5 × 10−4) by Kaplan–Meier analysis. In the COEUR cohort, the E-CADH-KRT7 signature was a strong independent prognostic biomarker (OS, HR = 1.6, p = 2.9 × 10−4; PFS, HR = 1.3, p = 0.008) and predicted a poor patient response to chemotherapy (p = 1.3 × 10−4). Our results identify a combination of two epithelial markers as highly significant indicators of HGSC patient prognosis and treatment response.

show abstract

“…In addition, several novel FOXM1 gene targets have been identified in ovarian cancer. For example, the cytoskeleton proteins cytokeratin-5 ( KRT5 ) and cytokeratin-7 ( KRT7 ) are known to promote migration in SKOV3 cells [ 226 ]. DLX1 [ 224 ], PCLAF [ 225 ], KIF20A [ 223 ], and CTNNB1 [ 229 ] have been shown to contribute to proliferation and metastatic phenotypes.…”

Section: Foxm1 Oncogenic Functionsmentioning

confidence: 99%

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

Liu

Barger

Karpf

2021

Cancers

View full text Add to dashboard Cite

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.

show abstract

FoxM1 promotes the migration of ovarian cancer cell through KRT5 and KRT7

Cited by 38 publications

References 32 publications

MicroRNA‐216a targets WT1 expression and regulates KRT7 transcription to mediate the progression of pancreatic cancer—A transcriptome analysis

MicroRNA‐216a targets WT1 expression and regulates KRT7 transcription to mediate the progression of pancreatic cancer—A transcriptome analysis

A Keratin 7 and E-Cadherin Signature Is Highly Predictive of Tubo-Ovarian High-Grade Serous Carcinoma Prognosis

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

Contact Info

Product

Resources

About