scholarly journals The role of Sox6 and Netrin-1 in ovarian cancer cell growth, invasiveness, and angiogenesis

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770550 ◽  
Author(s):  
Yi Li ◽  
Ming Xiao ◽  
Fangchun Guo
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Conditioned Medium ◽  
Umbilical Vein ◽  
Inhibitory Effect ◽  
Ovarian Cancer Cells ◽  
Human Umbilical Vein ◽  
Tumor Tissues

SOX6 plays important roles in cell proliferation, differentiation, and cell fate determination. It has been confirmed that SOX6 is a tumor suppressor and downregulated in various cancers, including esophageal squamous cell carcinoma, hepatocellular carcinoma, and chronic myeloid leukemia. Netrin-1 is highly expressed in various human cancers and acts as an anti-apoptotic and proangiogenic factor to drive tumorigenesis. The role of SOX6 and netrin-1 in regulating the growth of ovarian tumor cells still remains unclear. Real-time polymerase chain reaction and western blot were used to determine the SOX6 messenger RNA and protein levels, respectively, in ovarian cancer cells and tumor tissues. Stable transfection of SOX6 was conducted to overexpress SOX6 in PA-1 and SW626 cells. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Invasion of ovarian cancer cells and migration of human umbilical vein endothelial cells were confirmed by Transwell assays. To overexpress netrin-1, ovarian cancer cells with SOX6 restoration was transduced with netrin-1 lentiviral particles. PA-1 xenografts in a nude mice model were used to conduct in vivo evaluation of the role of SOX6 and its relationship with netrin-1 in tumor growth and angiogenesis. In this study, we found significantly reduced SOX6 levels in PA-1, SW626, SK-OV-3, and CaoV-3 ovarian cancer cell lines and human tumor tissues in comparison with normal human ovarian epithelial cells or matched non-tumor tissues. SOX6 overexpression by stable transfection dramatically inhibited proliferation and invasion of PA-1 and SW626 cells. Also, conditioned medium from PA-1 and SW626 cells with SOX6 restoration exhibited reduced ability to induce human umbilical vein endothelial cells migration and tube formation compared with conditioned medium from the cells with transfection control. Furthermore, an inverse relationship between SOX6 and netrin-1 expression was observed in PA-1 and SW626 cells. Overexpression of netrin-1 in ovarian cancer cells with forced SOX6 expression remarkably abrogated the inhibitory effect of SOX6 on proliferation, invasion of the cells, and tumor xenograft growth and vascularity in vivo. Human umbilical vein endothelial cell migration and tube formation were enhanced in the conditioned medium from the ovarian cancer cells transduced with netrin-1 lentivirus particles. Our observations revealed that SOX6 is a tumor suppressor in ovarian cancer cells, and SOX6 exerts an inhibitory effect on the proliferation, invasion, and tumor cell-induced angiogenesis of ovarian cancer cells, whereas nerin-1 plays an opposite role and its expression is inversely correlated with SOX6. Moreover, our findings suggest a new role of SOX6 and netrin-1 for understanding the progression of ovarian cancer and have the potential for the development of new diagnosis and treatment strategies for ovarian cancer.

Complement Component 3 (C3) Is a Mediator of Epithelial-Mesenchymal Transition (EMT)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1421-1421
Author(s):  
Min Soon Cho ◽  
Qianghua Hu ◽  
Rajesha Rupaimoole ◽  
Anil Sood ◽  
Vahid Afshar-Kharghan
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Tumors ◽  
Mouse Embryos ◽  
Ovarian Cancer Cells ◽  
Mesenchymal Transition ◽  
E Cadherin

Abstract We have shown that complement component 3 (C3) is expressed in malignant ovarian epithelial cells and enhances cell proliferation in vitro and tumor growth in vivo. C3 is secreted by cancer cells into the tumor microenvironment and promotes tumor growth through an autocrine loop. To understand the mechanism of upregulation of C3 expression in malignant epithelial cells, we studied the transcriptional regulation of C3, and found that TWIST1, a major regulator of EMT, binds to the C3 promoter and regulates C3 transcription. Knockdown of the TWIST1 gene reduced C3 mRNA, and TWIST1 overexpression increased C3 mRNA. TWIST1 promotes epithelial-mesenchymal transition (EMT) during normal development and in metastasis of malignant tumors. An important marker of EMT is a reduction in the surface expression of E-cadherin on cells facilitating migration and invasion of these cells. TWIST1 is a transcriptional repressor of E-cadherin; and because TWIST1 increases C3 expression, we investigated whether C3 is also a negative regulator of E-cadherin expression. We overexpressed C3 in ovarian cancer cells by stable transduction of lentivirus carrying C3 cDNA. Overexpression of C3 was associated with 32% reduction in the expression of E-cadherin resulting in enhanced migration ability of cells by 2.3 folds and invasiveness by 1.75 folds, as compared to control cells transduced with control lentivirus. To investigate whether TWIST1-induced reduction in E-cadherin is C3-mediated or not, we studied the effect of TWIST1 overexpression simultaneous with C3 knockdown in ovarian cancer cells. Overexpression of TWIST1 alone resulted in 70% reduction in E-cadherin mRNA and this was completely reversed after simultaneous C3 knockdown in these cells. To investigate the correlation between C3 and TWIST1 in vivo, we studied the co-expression of these two proteins in mouse embryos (physiologic EMT) and in malignant tumors (pathologic EMT). Given the role of EMT in embryogenesis we immunostained mouse embryos at different stages of development, using antibodies against TWIST1 or C3. Transverse section of 9.5-day post-coitum (9.5dpc) mouse embryos showed co-expression of TWIST1 and C3 in otocyst (ot) and hindbrain (hb) of neural crest. In the whole-mounted 11.5dpc mouse embryos, C3 and TWIST1 were co-expressed in limb buds. Given the role of EMT in malignancy, tumors induced in mice after intraperitoneal injection of murine ovarian cancer cells were resected and immunostained for C3 and TWIST1 proteins. TWIST1 and C3 co-localized at tumor edges, where EMT and tumor cells migration occur. Taken together, these data provide evidence that TWIST1 regulates C3 expression, and C3 promotes EMT through E-cadherin. Disclosures No relevant conflicts of interest to declare.

scholarly journals An Effective Inhibitory Strategy of Low Steady Magnetic Field on Ovarian Cancer

2021 ◽  
Author(s):  
Xiaodi Li ◽  
Yanwen Fang ◽  
Zhicai Fang ◽  
Ping Wang ◽  
Jun Zhu
Keyword(s):  
Magnetic Field ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Model ◽  
Inhibitory Effect ◽  
Ovarian Cancer Cells ◽  
Magnetic Intensity ◽  
Ovarian Cancer Cell Lines

Abstract To estimate the effect of a steady-state magnetic field (SMF) with low magnetic intensity gradient on the apoptosis-promoting factors related to cancer cells, we systematically select SMF with 0.2T, 0.4T and 0.6T to study their effect on different ovarian cancer lines. An in vitro cell model system about two kinds of ovarian cancer lines is established, whose viability and intracellular factors are detected by CCK-8, confocal microscopy and flow cytometry method. The results demonstrate that the apoptosis rate of ovarian cancer cells is increased with the enhancement of SMF magnetic intensity. Furthermore, we detect an increasing ROS and intracellular Ca2+ levels in ovarian cancer cells, which can be caused by SMF. The results suggest that ROS and Ca2+ levels are the main reason for the significant apoptosis of ovarian cancer cell lines in SMF. Moreover, an in vivo experiment also reveals that SMF has a strong inhibitory effect on ovarian cancer. Therefore, the inhibitory strategy is an effective, which has a great potential in the treatment of drug-resistant ovarian cancer.

scholarly journals Long Noncoding RNA E2F4as Promotes Progression and Predicts Patient Prognosis in Human Ovarian Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3626
Author(s):  
Sun-Ae Park ◽  
Lee Kyung Kim ◽  
Young Tae Kim ◽  
Tae-Hwe Heo ◽  
Hee Jung Kim
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Noncoding Rna ◽  
Ovarian Cancer Cells ◽  
Serum Samples ◽  
Invasion And Migration ◽  
In Vivo Experiments

(1) Background: LncRNAs could be a promising biomarker to predict the prognosis of various cancers. The significance of E2F4antisense lncRNA remains unclear in cancer. In this study, we examined the expression level of E2F4as in the serum of ovarian cancer patients and the functional role of E2F4as. (2) Methods: Serum samples were obtained from 108 OC patients and 32 normal patients to measure the expression of E2F4as in the serum. Ovarian cancer cells were used to investigate the role of E2F4as in cell proliferation, invasion, migration and apoptosis, and the expression of E2F4as was knocked down using RNA interference. In addition, E2F4as knockdown cell lines were used in in vivo experiments. (3) Results: The expression of E2F4as was significantly higher in the serum of OC patients than in that of control patients (p < 0.05). The knockdown of E2F4as in ovarian cancer cells led to a decrease in cell proliferation, invasion and migration and an increase in apoptosis. E2F4as knockdown also reduced the expression of epithelium–mesenchymal metastasis (EMT) genes. (4) Conclusion: These findings highlight the clinical significance of E2F4as in predicting the prognosis of OC patients and suggest its potential in promoting tumour aggressiveness by the regulation of EMT-related mechanisms.

scholarly journals WISP2 promotes cell proliferation via targeting ERK and YAP in ovarian cancer cells

2020 ◽  
Author(s):  
Zi-Qing Shi ◽  
Zi-Yan Chen ◽  
Yao Han ◽  
Heng-Yan Zhu ◽  
Meng-Dan Lyu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Inhibitory Effect ◽  
Ovarian Cancer Cells ◽  
Extracellular Signal ◽  
And Migration

Abstract Background: Wnt-inducible signaling pathway protein 2 (WISP2) is a wnt1-induced signaling pathway protein 2. Although studies indicate that WISP2 may promote the development of various tumors, its role in ovarian cancer remains unclear. The objective of the current study was to analyze the effects of WISP2 on the proliferation and migration of ovarian cancer cells in vitro and in vivo.Results: Immunohistochemistry and western blotting indicated that WISP2 was highly expressed in various ovarian cancer tissues and cell lines，but weakly expressed in normal ovary tissue. WISP2 deletion inhibited cell growth, clone formation, and migration of ovarian cancer cells while promoting cell apoptosis and affecting the cell cycle. This growth inhibitory effect caused by WISP2 loss is due to the inhibition of phosphorylated extracellular signal-related kinase (p-ERK)1/2, as well as CCAAT/enhancer-binding protein α (CEBPα) and CEPBβ. In addition, WISP2 deletion also activated the Yes-associated protein (YAP).Conclusion: WISP2 deletion inhibits ovarian cancer cell proliferation by affecting ERK signaling pathways.

scholarly journals WISP2 promotes cell proliferation via targeting ERK and YAP in ovarian cancer cells

2020 ◽  
Author(s):  
Zi-Qing Shi ◽  
Zi-Yan Chen ◽  
Yao Han ◽  
Heng-Yan Zhu ◽  
Meng-Dan Lyu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Inhibitory Effect ◽  
Ovarian Cancer Cells ◽  
Growth Inhibitory ◽  
Extracellular Signal ◽  
And Migration

Abstract Background Wnt inducible signaling protein 2 (WISP2) is a wnt1-induced signaling pathway protein 2. Although studies indicate that WISP2 may promote the development of various tumors, its role in ovarian cancer remains unclear. The objective of the current study was to analyze the effects of WISP2 on proliferation and migration of ovarian cancer cells in vitro and in vivo . Results Immunohistochemistry and western blot results indicated that WISP2 was highly expressed in various ovarian tissues and cell lines. WISP2 deletion inhibited cell growth, clone formation, and migration of ovarian cancer cells. WISP2 deletion promoted cell apoptosis and affected the cell cycle. This growth inhibitory effect caused by WISP2 loss is due to the inhibition of extracellular signal-related kinase (p-ERK)1/2, as well as CEBPα and CEBPβ. In addition, WISP2 deletion also activated the Yes-associated protein (YAP). Conclusion WISP2 deletion inhibits ovarian cancer cell proliferation by affecting ERK signaling pathways.

Inhibitory Effect of the Zinc Metallochaperone NSC319726 on Ovarian Cancer Cells via the Regulation of P53

2021 ◽  
Author(s):  
Shikui Sun ◽  
Yue Liang ◽  
Ke Li ◽  
Yizhen Wang ◽  
Huimin Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Suppressor Gene ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Cyclin Dependent Kinase ◽  
Tumor Protein P53 ◽  
Novel Drug

Abstract Ovarian cancer is the leading cause of death from malignancies of the female reproductive system. In recent years, there has been little development regarding the treatment of ovarian cancer. Wild-type tumor protein p53 (P53) can inhibit the development of tumor, however, mutations in P53 have been shown in most cases of ovarian cancer. The mutated gene encoded P53 transforms from a tumor suppressor gene to an oncogene, losing its original anti-tumor function. Studies have shown that the zinc metallochaperone NSC319726 can promote the correct folding of P53 in cancer cells and restore its physiological function, however, the function of NSC319726 in ovarian cancer has not been elaborated. So we investigated the role of NSC319726 on biological functions of ovarian cancer and preliminarily determined the specific molecular mechanism. The results showed that NSC319726 could inhibit proliferation, migration and invasion of ovarian cancer cells and promote their apoptosis. Mechanically, NSC319726 regains the tumor-suppressed function of P53, further activates the downstream cyclin-dependent kinase CDK inhibited protein P21, thereby blocking the cell cycle and inhibiting cells proliferation. Therefore, NSC319726 has the potential to act as a novel drug for treating ovarian cancer.

scholarly journals RAC1/miR-3613/RAC1 feedback loop contributes to ovarian cancer progression

2021 ◽  
Author(s):  
Changzhong Li ◽  
Ruobing Leng ◽  
Yunfang Meng ◽  
Na Li ◽  
Feifei Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Inhibitory Effect ◽  
Ovarian Cancer Cells ◽  
Negative Feedback Loop

Abstract The RAC1 signal pathway is involved in various tumor cell biological processes. Here, the role of RAC1-miR-3613-RAC1 negative feedback loop in ovarian cancer was explored. Results showed that RAC1 knockdown up-regulated miR-3613, which in turn inhibited RAC1 expression. RAC1 counteracted the inhibitory effect of miR-3613 on the proliferation and invasion of ovarian cancer cells in vitro and on the tumor growth in vivo. In ovarian cancer, miR-3613 expression was negatively correlated with RAC1, and patients with low miR-3613 expression had poor prognosis. These findings indicate the role of RAC1-miR-3613-RAC1 negative feedback loop in the malignant progression of ovarian cancer and its possible therapeutic values.

scholarly journals Adipose-Derived Mesenchymal Stem Cells Enhance Ovarian Cancer Growth and Metastasis by Increasing Thymosin Beta 4X-Linked Expression

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Yijing Chu ◽  
Min You ◽  
Jingjing Zhang ◽  
Guoqiang Gao ◽  
Rendong Han ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cancer Cells ◽  
Conditioned Medium ◽  
Normal Growth ◽  
Underlying Mechanism ◽  
Ovarian Cancer Cells ◽  
Promoting Effect

As shown in our previous studies, growth and metastasis of ovarian cancer can be regulated by adipose-derived mesenchymal stem cells (ADSCs). However, the underlying mechanism has not yet been revealed. In this study, a proteomics analysis was performed to compare protein expression treated with and without ADSCs in ovarian cancer cells. Protein levels were altered in ovarian cancer cells due to the treatment of ADSCs. Thymosin beta 4 X-linked (TMSB4X) levels changed dramatically, and this protein was identified as one of the most important candidate molecules contributing to the tumour-promoting effects of ADSCs. Compared with the cells that are cultured in the normal growth medium, the TMSB4X levels cultured in ADSC-conditioned medium increased significantly in ovarian cancer cells. Furthermore, the growth and invasion of cancer cells were decreased, even in the ADSC-conditioned medium treatment group (P<0.05), by the inhibition of TMSB4X. As shown in the bioluminescence images captured in vivo, increased ovarian cancer’s growth and metastasis, along with elevated TMSB4X expression, were observed in the group of ADSC-conditioned medium, and the tumour-promoting effect of ADSCs was attenuated by the inhibition of TMSB4X. Based on our findings, increased TMSB4X expression may play a role in accelerating the ADSC-mediated proliferation, invasion, and migration of ovarian cancers.

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