FOXC2 promotes chemoresistance in nasopharyngeal carcinomas via induction of epithelial mesenchymal transition

Zhou, Zhijiao; Zhang, Lu; Xie, Bowen; Wang, Xiangpu; Yang, Xinhui; Ding, Nianhua; Zhang, Jing; Liu, Qingqing; Tan, Guolin; Feng, Daxiong; Sun, Lun‐Quan

doi:10.1016/j.canlet.2015.04.008

Cited by 71 publications

(56 citation statements)

References 35 publications

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“…The human NPC 5-8F and CNE2 cell lines were provided by the Research Center of Clinical Oncology of the Affiliated Jiangsu Cancer Hospital (Nanjing Medical University, Nanjing, China). Although it was reported that the CNE2 cell line was potentially contaminated on September 2014 (19), several studies based on this cell line have been published afterwards (20)(21)(22)(23), which seem to support the authors' view that the misidentification issue was unlikely to affect the outcomes of the present study.…”

Section: Methodssupporting

confidence: 79%

MIIP gene expression is associated with radiosensitivity in human nasopharyngeal carcinoma cells

et al. 2018

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Abstract. The present study aims to investigate the radiosensitization effect of the migration and invasion inhibitory protein (MIIP) gene on nasopharyngeal carcinoma (NPC) cells. The MIIP gene was transfected into NPC 5-8F and CNE2 cells. The level of MIIP was analyzed by quantitative reverse transcription-polymerase chain reaction analysis and western blot. The changes in radiosensitivity of the cells were analyzed by colony formation assay. The changes in cell apoptosis and cycle distribution following irradiation were detected by flow cytometry. The expression of BCL2 associated X, apoptosis regulator/B-cell lymphoma 2 was evaluated using western blot. DNA damage was analyzed by counting γ-H2AX foci. The expression levels of γ-H2AX were evaluated by immunofluorescence and western blot. In a previous study by the authors, the results indicated that the expression of MIIP gene evidently increased in MIIP-transfected 5-8F (5-8F OE) and MIIP-transfected CNE2 (CNE2 OE) cells compared with the parental or negative control cells. In the present study, the survival rate of 5-8F OE and CNE2 OE cells markedly decreased following irradiation (0, 2, 4, 6 and 8 Gy) compared with the negative control (5-8F NC and CNE2 NC) and the untreated (5-8F and CNE2) groups. The expression of MIIP was able to increase apoptosis, which resulted in G2/M cell cycle arrest and DNA damage repair was attenuated in 5-8F and CNE2 cells following irradiation as measured by the accumulation of γ-H2AX. It was indicated that MIIP expression is associated with the radiosensitivity of NPC cells and has a significant role in regulating cell radiosensitivity.

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Section: Methodssupporting

confidence: 79%

MIIP gene expression is associated with radiosensitivity in human nasopharyngeal carcinoma cells

et al. 2018

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“…Importantly, the correlations between FOXC2 and tumor chemoresistance are also reported. Zhou et al showed that FOXC2 could promote chemoresistance in nasopharyngeal carcinomas via induction of epithelial mesenchymal transition [31]. Also, Yang et al reported that downregulation of Foxc2 could enhance apoptosis induced by 5-fluorouracil in colorectal cancer [32].…”

Section: Discussionmentioning

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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“…EMT is a critical step during embryo development, wound healing, tissue fibrosis, tumor migration, and invasion [15-16]. As a dynamic and reversible process, the EMT progression, characterized by an alteration in cellular morphology, enhancement in the mobile ability, formation of a cancer stem cell (CSC) phenotype, and acquisition of anoikis resistance, was detected in certain drug-resistant cancer cells such as hepatocellular carcinoma [17], colorectal cancer [18], nasopharyngeal carcinoma [19], and breast cancer [20]. Concomitantly, downregulation of the epithelial marker (E-cadherin) and upregulation of mesenchymal markers (vimentin, N-cadherin, fibronectin) and other related transcription factors (snail, slug, and twist) were also found in drug-resistant cancer cells with an EMT phenotype [12].…”

Section: Introductionmentioning

confidence: 99%

CNTN-1 Enhances Chemoresistance in Human Lung Adenocarcinoma Through Induction of Epithelial-Mesenchymal Transition by Targeting the PI3K/Akt Pathway

Zhang

Sun

et al. 2017

Cell Physiol Biochem

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Background/Aims: Chemoresistance has been a major obstacle to the effective treatment of lung cancer. Previously, we found that contactin-1 (CNTN-1) is related to cisplatin resistance in lung adenocarcinoma. Here, we aimed to investigate the underlying mechanism behind the role of CNTN-1 in cisplatin resistance in lung adenocarcinoma. Methods: EMT-associated phenotypes, including alterations in cellular morphology and marker (E-cadherin, N-cadherin and Vimentin) expression, were compared between A549 cells and A549/DDP cells (a cisplatin-resistant cell line of lung adenocarcinoma with abnormal CNTN-1 expression) by using real-time time PCR and Western blotting. Other methods, including CNTN-1 overexpression in A549 cells and CNTN-1 knockdown in A549/DDP cells, were also used to investigate the role of CNTN-1 in mediating the EMT phenotype and thr resulting cisplatin resistance and malignant progression of cancer cells in vitro and in vivo. Results: A549/DDP cells exhibited an EMT phenotype and aggravated malignant behaviors. CNTN-1 knockdown in A549/DDP cells partly reversed the EMT phenotype, increased drug sensitivity, and attenuated the malignant progression whereas CNTN-1 overexpression in A549 cells resulted in the opposite trend. Furthermore, the PI3K/Akt pathway was involved in the effects of CNTN-1 on EMT progression in A549/DDP cells, verified by the xenograft mouse model. Conclusion: CNTN-1 promotes cisplatin resistance in human cisplatin-resistant lung adenocarcinoma through inducing the EMT process by activating the PI3K/Akt signaling pathway. CNTN-1 may be a potential therapeutic target to reverse chemoresistance in cisplatin-resistant lung adenocarcinoma.

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FOXC2 promotes chemoresistance in nasopharyngeal carcinomas via induction of epithelial mesenchymal transition

Cited by 71 publications

References 35 publications

MIIP gene expression is associated with radiosensitivity in human nasopharyngeal carcinoma cells

MIIP gene expression is associated with radiosensitivity in human nasopharyngeal carcinoma cells

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

CNTN-1 Enhances Chemoresistance in Human Lung Adenocarcinoma Through Induction of Epithelial-Mesenchymal Transition by Targeting the PI3K/Akt Pathway

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