High Expression of Forkhead Box Protein C2 is Related to Poor Prognosis in Human Gliomas

Wang, Yaowu; Yin, Chunli; Zhang, Hongyi; Hao, Jinmin; Yang, Yue-Ye; Liao, Heng; Jiao, Baohua

doi:10.7314/apjcp.2014.15.24.10621

Cited by 15 publications

(12 citation statements)

References 16 publications

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“…Ectopic expression of FOXC2 has been found to participate in tumorigenesis and the development of human malignances. 13 A high expression level of FOXC2 has been found to be a prognostic factor in gliomas, 14 nasopharyngeal cancer, 15 and gastric cancer. 16 In addition, FOXC2 has been reported to regulate chemosensitivity in some human cancers.…”

Section: Introductionmentioning

confidence: 99%

<p>FOXC2 Promotes Oxaliplatin Resistance by Inducing Epithelial-Mesenchymal Transition via MAPK/ERK Signaling in Colorectal Cancer</p>

Chen¹,

Deng²,

Fu³

et al. 2020

OTT

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Background: Chemoresistance is a major obstacle to improving the survival rate of colorectal cancer (CRC) patients. Forkhead box protein C2 (FOXC2), a member of the forkhead box (Fox) transcription factor family, is reported to be an important regulator of epithelial-tomesenchymal transition (EMT) and plays a key role in tumor progression. However, little is known about the effects of FOXC2 on oxaliplatin (OXA) resistance in CRC. Methods: OXA-resistant cells were generated from HCT116 cells. CCK-8, colony formation, flow cytometry and Transwell assays were used to compare the characteristics of OXAresistant HCT116/OXA cells and the corresponding parental HCT116 cells. The expression of FOXC2 was confirmed by qRT-PCR and Western blotting in HCT116/OXA and HCT116 cells. Gain-and loss-of-function assays were performed to evaluate the effects of FOXC2 on OXA sensitivity and EMT in HCT116/OXA and HCT116 cells both in vitro and in vivo, and the possible molecular mechanisms were investigated. Results: The relative expression of FOXC2 was significantly increased in HCT116/OXA cells compared with the parental HCT116 cells. Upregulation of FOXC2 in HCT116 cells reduced OXA sensitivity and promoted EMT. However, knockdown of FOXC2 in HCT116/OXA cells markedly increased the in vitro and in vivo sensitivity of HCT116/OXA cells to OXA by regulating EMT progression. Furthermore, FOXC2 activated MAPK/ERK signaling, and blockade of ERK attenuated FOXC2-induced EMT and FOXC2-enhanced OXA resistance. Conclusion: FOXC2 induced EMT to promote oxaliplatin resistance by activating the MAPK/ERK signaling pathway. FOXC2 may be a potential therapeutic target for overcoming OXA resistance in human CRC.

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Section: Introductionmentioning

confidence: 99%

<p>FOXC2 Promotes Oxaliplatin Resistance by Inducing Epithelial-Mesenchymal Transition via MAPK/ERK Signaling in Colorectal Cancer</p>

Chen¹,

Deng²,

Fu³

et al. 2020

OTT

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“…Also, haplodeficiency of FOXC2 could lead to impaired formation of tumor blood vessels as well as reduced tumor growth, suggesting that FOXC2 is critical for tumor development and angiogenesis. Meanwhile, high expression of FOXC2 is reported to be an independent prognostic factor in glioma, esophageal cancer, gastric cancer and non-small cell lung cancer [10][11][12][13]. Recently, overexpressed FOXC2 is found to enhance the epithelial-to-mesenchymal transition and invasion of ovarian cancer cells [14].…”

Section: Introductionmentioning

confidence: 99%

Forkhead Box Protein C2 (FOXC2) Promotes the Resistance of Human Ovarian Cancer Cells to Cisplatin In Vitro and In Vivo

Ding

Tian

et al. 2016

Cell Physiol Biochem

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Background/Aims: FOXC2 has been reported to play a role in tumor progression, but the correlations of FOXC2 with the cisplatin (CDDP) resistance of ovarian cancer cells are still unclear. The purpose of the present study is to investigate the roles of FOXC2 in the CDDP resistance of ovarian cancer cells and its possible mechanisms. Methods: Quantitative real-time PCR (qRT-PCR) was performed to detect the expression of FOXC2 mRNA in CDDP-resistant or sensitive ovarian cancer tissues and cell lines (SKOV3/CDDP and SKOV3). Gain- and loss-of-function assays were performed to analyze the effects of FOXC2 knockdown or overexpression on the in vitro and in vivo sensitivity of ovarian cancer cells to CDDP and its possible molecular mechanisms. Results: The relative expression level of FOXC2 mRNA in CDDP-resistant ovarian cancer tissues was higher than that in CDDP-sensitive tissues. Also, the expression of FOXC2 mRNA and protein in CDDP-resistant ovarian cancer cell line (SKOV3/CDDP) cell line was higher than that in its parental cell line (SOKV3). Small hairpin RNA (shRNA)-mediated FOXC2 knockdown significantly increased the in vitro and in vive sensitivity of SKOV3/CDDP cells to CDDP by enhancing apoptosis, while upregulation of FOXC2 significantly decreased the in vitro and in vivo sensitivity of SKOV3 cells to CDDP by reducing apoptosis. Furthermore, FOXC2 activates the Akt and MAPK signaling pathways, and then induced the decreased expression of Bcl-2 protein and the increased expression of Bax and cleaved caspase-3 proteins. Conclusions: FOXC2 mediates the CDDP resistance of ovarian cancer cells by activation of the Akt and MAPK signaling pathways, and may be a potential novel therapeutic target for overcoming CDDP resistance in human ovarian cancer.

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“…A total of 2115 patients in 15 studies were recruited. 2 – 16 The following details were extracted: the first author’s last name, publication year, study country, pathology type, patient age, sex ratio, tumor stage, detection method, numbers of patients, source of HR, analysis model, follow-up and HRs with 95% confidence interval (CIs) for OS, cancer-specific survival (CSS), or disease-free survival (DFS). The HRs and corresponding 95% CIs were extracted preferentially from multivariate analyses when available.…”

Section: Methodsmentioning

confidence: 99%

“…Published studies have indicated that high expression of FOXC2 is negatively correlated with overall survival (OS) for tumors, including pancreatic cancer, esophageal squamous cell carcinoma, human gliomas, colon cancer, hepatocellular carcinoma, and pulmonary neuroendocrine tumors. 2 – 7 In contrast, some researchers have reported that FOXC2 has a lesser association with OS in human gliomas, non-small-cell lung cancer, and hepatocellular carcinoma. 8 , 9 Therefore, we conducted this meta-analysis to illuminate the prognostic value of FOXC2 in various tumors.…”

Section: Introductionmentioning

confidence: 99%

Meta-analysis of the prognostic significance of FOXC2 in various tumors

Tian

Liu

2019

J Int Med Res

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Objective Many studies have focused on correlations between forkhead box protein C2 (FOXC2) and various tumors but discrepant results have been reported. Thus, we conducted this meta-analysis to assess the prognostic role of FOXC2 in tumors. Methods Four electronic databases (PubMed, Embase, Web of Science, and SinoMed) were screened through September 2019. Results The final analysis included 15 reports and 2115 patients; results suggested that cancer patients with FOXC2 had worse overall survival (hazard ratio 2.14, 95% confidence interval (CI) 1.74–2.64), cancer-specific survival (hazard ratio 2.65, 95% CI 1.44–4.89), and disease-free survival (hazard ratio 1.93, 95% CI 1.49–2.50) than patients lacking FOXC2. Conclusions The presence of FOXC2 was associated with poor survival in cancer patients. FOXC2 could be a promising prognostic marker in the future.

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High Expression of Forkhead Box Protein C2 is Related to Poor Prognosis in Human Gliomas

Cited by 15 publications

References 16 publications

<p>FOXC2 Promotes Oxaliplatin Resistance by Inducing Epithelial-Mesenchymal Transition via MAPK/ERK Signaling in Colorectal Cancer</p>

<p>FOXC2 Promotes Oxaliplatin Resistance by Inducing Epithelial-Mesenchymal Transition via MAPK/ERK Signaling in Colorectal Cancer</p>

Forkhead Box Protein C2 (FOXC2) Promotes the Resistance of Human Ovarian Cancer Cells to Cisplatin In Vitro and In Vivo

Meta-analysis of the prognostic significance of FOXC2 in various tumors

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