Bisphenol A and Nonylphenol Have the Potential to Stimulate the Migration of Ovarian Cancer Cells by Inducing Epithelial–Mesenchymal Transition via an Estrogen Receptor Dependent Pathway

Tripartite motif 16 (TRIM16), a member of the RING B-box coiled-coil (RBCC)/tripartite motif (TRIM) protein family, has been shown to play a role in tumor development and progression. However, the role of TRIM16 in ovarian cancer has never been revealed. Thus, in this study, we investigated the roles and mechanisms of TRIM16 in ovarian cancer. Our results demonstrated that TRIM16 expression was low in ovarian cancer cell lines. In addition, overexpression of TRIM16 significantly inhibited the migration and invasion in vitro, as well as suppressed the epithelial‐mesenchymal transition (EMT) phenotype in ovarian cancer cells. Furthermore, overexpression of TRIM16 greatly inhibited the protein expression levels of Shh, Smo, Ptc, Gli-1, MMP2, and MMP9 in ovarian cancer cells. Taken together, these results strongly suggest that TRIM16 inhibits the migration and invasion via suppressing the Sonic hedgehog signaling pathway in ovarian cancer cells. Thus, TRIM16 may be a novel potential therapeutic target for ovarian cancer.

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FSCN1 Promotes Epithelial-Mesenchymal Transition Through Increasing Snail1 in Ovarian Cancer Cells

Cellular Physiology and Biochemistry ◽

10.1159/000493622 ◽

2018 ◽

Vol 49 (5) ◽

pp. 1766-1777 ◽

Cited By ~ 8

Author(s):

Jie Li ◽

Songlin Zhang ◽

Meili Pei ◽

Lei Wu ◽

Yanli Liu ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cancer Progression ◽

Epithelial Mesenchymal Transition ◽

Ovarian Cancer Cell ◽

Ovarian Cancer Cells ◽

Transwell Assay ◽

Mesenchymal Transition ◽

Novel Target ◽

Snail1 Expression

Background/Aims: Epithelial-mesenchymal transition (EMT) is one of the key mechanisms mediating cancer progression. Snail1 has a pivotal role in the regulation of EMT, involving the loss of E-cadherin and concomitant upregulation of vimentin, among other biomarkers. We have found FSCN1 promoted EMT in ovarian cancer cells, but the precise mechanism of FSCN1 in EMT process has not been clearly elucidated. Methods: The levels of FSCN1 and snail1 were determined in epithelial ovarian cancer(EOC) specimen and in ovarian cancer cells by RT-qPCR. The changes of EMT makers and effects on snail1 by FSCN1 were examined by overexpression or depletion of FSCN1 in EOC cells by RT-qPCR and western blotting. The invasiveness of the FSCN1-modified EOC cells was examined in transwell assay. Co-immunoprecipitation (IP) was performed to detect the interaction between snail1 and FSCN1 in EOC cells. Results: We found FSCN1 and snail1 significantly increased in EOC, and especially in EOC with metastasis. FSCN1 was positively correlated with snail1 expression at the cellular/histological levels. Moreover, we further showed that FSCN1 physiologically interacted with and increased the levels of snail1 to promote ovarian cancer cell EMT. Conclusion: FSCN1 promote EMT through snail1 in ovarian cancer cells. FSCN1 is an attractive novel target for inhibiting invasion and metastasis of EOC cells.

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Notch3 induces epithelial–mesenchymal transition and attenuates carboplatin-induced apoptosis in ovarian cancer cells

Gynecologic Oncology ◽

10.1016/j.ygyno.2013.03.019 ◽

2013 ◽

Vol 130 (1) ◽

pp. 200-206 ◽

Cited By ~ 37

Author(s):

Nidhi Gupta ◽

Zhihua Xu ◽

Ahmed El-Sehemy ◽

Helen Steed ◽

YangXin Fu

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Ovarian Cancer Cells ◽

Mesenchymal Transition ◽

Induced Apoptosis

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Forkhead Box Protein C2 Promotes Epithelial-Mesenchymal Transition, Migration and Invasion in Cisplatin-Resistant Human Ovarian Cancer Cell Line (SKOV3/CDDP)

Cellular Physiology and Biochemistry ◽

10.1159/000447818 ◽

2016 ◽

Vol 39 (3) ◽

pp. 1098-1110 ◽

Cited By ~ 11

Author(s):

Chanjuan Li ◽

Hongjuan Ding ◽

Jing Tian ◽

Lili Wu ◽

Yun Wang ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cell Line ◽

Epithelial Mesenchymal Transition ◽

Ovarian Cancer Cell Line ◽

Cancer Cell Line ◽

Ovarian Cancer Cells ◽

Skov3 Cell ◽

Mesenchymal Transition ◽

Forkhead Box

Background/Aims: Forkhead Box Protein C2 (FOXC2) has been reported to be overexpressed in a variety of human cancers. However, it is unclear whether FOXC2 regulates epithelial-mesenchymal transition (EMT) in CDDP-resistant ovarian cancer cells. The aim of this study is to investigate the effects of FOXC2 on EMT and invasive characteristics of CDDP-resistant ovarian cancer cells and the underlying molecular mechanism. Methods: MTT, Western blot, scratch wound healing, matrigel transwell invasion, attachment and detachment assays were performed to detect half maximal inhibitory concentration (IC50) of CDDP, expression of EMT-related proteins and invasive characteristics in CDDP-resistant ovarian cancer cell line (SKOV3/CDDP) and its parental cell line (SKOV3). Small hairpin RNA (shRNA) was used to knockdown FOXC2 and analyze the effect of FOXC2 knockdown on EMT and invasive characteristics of SKOV3/CDDP cells. Also, the effect of FOXC2 upregulation on EMT and invasive characteristics of SKOV3 cells was analyzed. Furthermore, the molecular mechanism underlying FOXC2-regulating EMT in ovarian cancer cells was determined. Results: Compared with parental SKOV3 cell line, SKOV3/CDDP showed higher IC50 of CDDP (43.26μM) (P<0.01) and acquired EMT phenotype and invasive characteristics. Gain- and loss-of-function assays indicated that shRNA-mediated FOXC2 knockdown could reverse EMT and reduce the capacity of migration, invasion, attachment and detachment in SKOV3/CDDP cell line and upregulation of FOXC2 could induce the reverse effects in parental SKOV3 cell line. Furthermore, it was found that activation of ERK or AKT/GSK-3β signaling pathways was involved in FOXC2-promoting EMT in CDDP-resistant ovarian cancer cells. Conclusions: Taken together, these data demonstrate that FOXC2 may be a promoter of EMT phenotype in CDDP-resistant ovarian cancer cells and a potential therapeutic target for the treatment of advanced ovarian cancer.

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215 SNAIL AND SLUG, MARKERS OF EPITHELIAL MESENCHYMAL TRANSITION, APPEARED TO BE ALTERED BY ALKYL-PHENOLS, BISPHENOL A AND NONYL-PHENOL, IN OVARIAN CANCER CELLS EXPRESSING ESTROGEN RECEPTORS

Reproduction Fertility and Development ◽

10.1071/rdv27n1ab215 ◽

2015 ◽

Vol 27 (1) ◽

pp. 198 ◽

Cited By ~ 1

Author(s):

Y.-S. Kim ◽

K.-C. Choi

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Ovarian Cancer Cells ◽

Rt Pcr ◽

Nonyl Phenol ◽

Mesenchymal Transition ◽

And Migration ◽

Emt Markers ◽

E Cadherin

The ovary is the important organ to produce oocytes. Any disorder will affect embryo production. Ovarian cancer is one of gynecologic cancers in women which can affect ovarian functions. Oestradiol (E2) may be involved in ovarian cell growth and epithelial-mesenchymal transition (EMT) for diverse functions. EMT is an important process in embryo development and tumour migration or progression. Bis-phenol A (BPA) and nonyl-phenol (NP) have an estrogenic property, which can be suspected as endocrine disrupting chemicals (EDC). In this study, it has been examined whether BPA and NP can cause EMT process and migration in BG-1 ovarian cancer cells. To confirm the effect of these EDCs, BG-1 ovarian cancer cells were cultured and treated with DMSO (0.1%), E2 (10–7 M), BPA (10–6 M) and NP (10–6 M) for 0, 6, and 24 h. The mRNAs were extracted to perform reverse-transcription (RT)-PCR and the changes in the mRNA expressions were analysed by ANOVA test. Following treatments with BPA and NP, alterations of EMT markers; that is, vimentin and E-cadherin, were examined at mRNA levels by RT-PCR. The levels of vimentin were up-regulated by E2, BPA, or NP in a time-dependent manner. In addition, transcriptional factors of EMT response, i.e. snail and slug, were enhanced by these treatments more than 2 times. BG-1 cells were exposed to these EDCs for 0, 24, and 48 h. Vimentin and snail proteins were induced by E2, BPA, or NP, while the expression of E-cadherin was decreased by them. To reveal that this EMT response is affected by oestrogen receptor (ER), the cells were treated with these EDCs in the presence of an ER antagonist, ICI 182 780 (10–6 M). Treatment with ICI 182 780 reversed EDC-induced alteration of these EMT markers, E-cadherin, vimentin, and snail. Since EMT response can cause metastasis, a scratch assay was performed to show migration caused by BPA or NP. BPA or E2 enhanced migratory capability of these BG-1 cells. Taken together, these results indicate that BPA and NP, potential EDC, may have an ability to influence ovarian cancer metastasis via regulating snail and slug genes in ER-positive ovarian cancers. In a future study, their effects in inducing EMT and migration will be tested in a xenograft mouse model.This work was supported by a grant from the Next-Generation BioGreen 21 Program (no. PJ009599), Rural Development Administration, Republic of Korea.

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