Mesothelin enhances invasion of ovarian cancer by inducing MMP-7 through MAPK/ERK and JNK pathways

2012 ◽  
Vol 442 (2) ◽  
pp. 293-302 ◽  
Author(s):  
Ming-Cheng Chang ◽  
Chi-An Chen ◽  
Pao-Jen Chen ◽  
Ying-Cheng Chiang ◽  
Yu-Li Chen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Tumour Progression ◽  
Cancer Invasion ◽  
Mitogen Activated Protein Kinase ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Cancer Tissues ◽  
Specific Inhibitors

Ovarian cancer has one of the highest mortalities in malignancies in women, but little is known of its tumour progression properties and there is still no effective molecule that can monitor its growth or therapeutic responses. MSLN (mesothelin), a secreted protein that is overexpressed in ovarian cancer tissues with a poor clinical outcome, has been previously identified to activate PI3K (phosphoinositide 3-kinase)/Akt signalling and inhibit paclitaxel-induced apoptosis. The present study investigates the correlation between MSLN and MMP (matrix metalloproteinase)-7 in the progression of ovarian cancer, and the mechanism of MSLN in enhancing ovarian cancer invasion. The expression of MSLN correlated well with MMP-7 expression in human ovarian cancer tissues. Overexpressing MSLN or ovarian cancer cells treated with MSLN showed enhanced migration and invasion of cancer cells through the induction of MMP-7. MSLN regulated the expression of MMP-7 through the ERK (extracellular-signal-regulated kinase) 1/2, Akt and JNK (c-Jun N-terminal kinase) pathways. The expression of MMP-7 and the migrating ability of MSLN-treated ovarian cancer cells were suppressed by ERK1/2- or JNK-specific inhibitors, or a decoy AP-1 (activator protein 1) oligonucleotide in in vitro experiments, whereas in vivo animal experiments also demonstrated that mice treated with MAPK (mitogen-activated protein kinase)/ERK- or JNK-specific inhibitors could decrease intratumour MMP-7 expression, delay tumour growth and extend the survival of the mice. In conclusion, MSLN enhances ovarian cancer invasion by MMP-7 expression through the MAPK/ERK and JNK signal transduction pathways. Blocking the MSLN-related pathway could be a potential strategy for inhibiting the growth of ovarian cancer.

scholarly journals Tripartite Motif 16 Inhibits the Migration and Invasion in Ovarian Cancer Cells

2017 ◽  
Vol 25 (4) ◽  
pp. 551-558 ◽  
Author(s):  
Hongwei Tan ◽  
Jin Qi ◽  
Guanghua Chu ◽  
Zhaoyang Liu
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Hedgehog Signaling ◽  
Epithelial Mesenchymal Transition ◽  
Coiled Coil ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Mesenchymal Transition ◽  
Tripartite Motif

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.

scholarly journals Demethoxycurcumin inhibited human epithelia ovarian cancer cells’ growth via up-regulating miR-551a

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769430 ◽  
Author(s):  
Zhenhua Du ◽  
Xianqun Sha
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Natural Form ◽  
Ovarian Cancer Cell Lines ◽  
Induced Apoptosis ◽  
Tumor Suppressive Function ◽  
Cancer Tissues

Curcumin is a natural agent that has ability to dampen tumor cells’ growth. However, the natural form of curcumin is prone to degrade and unstable in vitro. Here, we demonstrated that demethoxycurcumin (a curcumin-related demethoxy compound) could inhibit cell proliferation and induce apoptosis of ovarian cancer cells. Moreover, IRS2/PI3K/Akt axis was inactivated in cells treated with demethoxycurcumin. Quantitative real-time reverse transcription polymerase chain reaction demonstrated that miR-551a was down-regulated in ovarian cancer tissues and ovarian cancer cell lines. Over-expression of miR-551a inhibited cell proliferation and induced apoptosis of ovarian cancer cells, whereas down-regulation of miR-551a exerted the opposite function. Luciferase assays confirmed that there was a binding site of miR-551a in IRS2, and we found that miR-551a exerted tumor-suppressive function by targeting IRS2 in ovarian cancer cells. Remarkably, miR-551a was up-regulated in the cells treated with demethoxycurcumin, and demethoxycurcumin suppressed IRS2 by restoration of miR-551a. In conclusion, demethoxycurcumin hindered ovarian cancer cells’ malignant progress via up-regulating miR-551a.

Critical role of SEMA5A expression in invasion and metastasis of ovarian cancer cell

2014 ◽  
Vol 2 (4) ◽  
pp. 247-259
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Critical Role ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Cancer Tissue ◽  
Invasion And Metastasis

Semaphorins are a large family of genes involved in the development and morphogenesis of the nervous system. SEMA5A has been reported as a bi-functional molecule, acting as both oncogene and tumor suppressor in different types of cancer. High expression levels of SEMA5A and its receptor, Plexin-B3, were associated with aggressiveness in pancreatic and prostate cancers. Our previous study in ovarian cancer metastasis indicates that FAK knock-down can suppress ovarian cancer cells migration and invasion. We hypothesized that SEMA5A expression promotes ovarian cancer invasion and metastasis. We investigated the expression of SEMA5A in patients with metastatic ovarian cancer (n = 43), localized tumor (n = 37) and normal ovarian tissue (n = 12) from non-malignant diseases as control with different histopathological characteristics. For Silencing of SEMA5A in vitro, we treated human ovarian cancer cells (OVCAR-3, A2780/CP70) with miR-27a and miR-27b. We observed significantly higher expression of SEMA5A protein (P= 0.001) in metastatic ovarian cancer tissue associated with poor overall survival outcomes compared to localized ovarian cancer and control. In vitro silencing of SEMA5A reduced migration and invasion of ovarian cancer cell. Our data offer opportunities for the therapeutic modulation and biomarker of metastatic ovarian cancer.

scholarly journals Effect of targeted silencing of IL-8 on in vitro migration and invasion of SKOV3 ovarian cancer cells

2016 ◽  
Vol 13 (2) ◽  
pp. 567-572 ◽  
Author(s):  
Yanyu Li ◽  
Ling Liu ◽  
Zeyuan Yin ◽  
Hui Xu ◽  
Shuang Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells

scholarly journals Emodin suppresses proliferation, migration and invasion in ovarian cancer cells by down regulating ILK in vitro and in vivo

2017 ◽  
Vol Volume 10 ◽  
pp. 3579-3589 ◽  
Author(s):  
Jingjing Lu ◽  
Ying Xu ◽  
Zhe Zhao ◽  
Xiaoning Ke ◽  
Xuan Wei ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells

scholarly journals Berberine inhibited metastasis through miR-145/MMP16 axis in vitro

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jie Li ◽  
Songlin Zhang ◽  
Lei Wu ◽  
Meili Pei ◽  
Yu Jiang
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Inhibition Of Proliferation ◽  
Reporter Assays ◽  
Polymerase Chain ◽  
Effective Component

AbstractOvarian cancer is the first leading cause of death in gynecological cancers. The continuous survival and metastasis of cancer cells are the main causes of death and poor prognosis in patients with ovarian cancer. Berberine is an effective component extracted from the rhizomes of coptis chinensis and phellodendron chinensis. In our study, we aim to explore the molecular mechanism underlying the regulation of proliferation, migration and invasion by berberine in ovarian cancer cells. CCK8 assay was used for detection of proliferative capacity of SKOV3 and 3AO cells. Wound healing assay was used to estimate cell migration and transwell assay was used to assess cell invasion. The mRNA expression of miR-145 and MMP16 were examined by quantitative real-time polymerase chain reaction (qRT-PCR). The protein level of MMP16 was detected by western blot analysis. In addition, luciferase reporter assays were used to demonstrate MMP16 was a target of miR-145. The results demonstrated berberine inhibited proliferation, migration and invasion, promoted miR-145 expression, and decreased MMP16 expression in SKOV3 and 3AO cells. MMP16 was a target of miR-145. Moreover, downregulation of MMP16 contributed to the inhibition of proliferation, migration and invasion by berberine. Together, our results revealed that berberine inhibited proliferation, migration and invasion through miR-145/MMP16 in SKOV3 and 3AO cells, highlighting the potentiality of berberine to be used as a therapeutic agent for ovarian cancer.

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

2016 ◽  
Vol 39 (1) ◽  
pp. 242-252 ◽  
Author(s):  
Chanjuan Li ◽  
Hongjuan Ding ◽  
Jing Tian ◽  
Lili Wu ◽  
Yun Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Mapk Signaling ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Cancer Tissues ◽  
Mapk Signaling Pathways

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.

scholarly journals ADAR1 Prevents R-loop Accumulation-Driven ATR Pathway Activation in Ovarian Cancer

2020 ◽  
Author(s):  
hanwei cui ◽  
Qian Yi ◽  
Min Tian ◽  
Yuteng Liang ◽  
Jie Huang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Pathway Activation ◽  
Rna Immunoprecipitation ◽  
Cancer Tissues

Abstract BackgroundAdenosine (A)-to-inosine (I) RNA editing is the most prevalent RNA editing mechanism, in which adenosine deaminases acting on RNA 1 (ADAR1) is a major adenosine deaminase. Increasing evidence suggests that editing dysregulation of ADAR1 plays an important role in human tumorigenesis, while the underlying mechanism remains elusive. MethodsThe clinical relevance of ADAR1 was analyzed by real-time PCR, western blotting and immunohistochemistry of ovarian cancer tissues. ADAR1 function on ovarian cancer cells in vitro were explored by colony formation assay, transwell assay and Brdu-based cell cycle assay in vitro and xenograft models in vivo. Western blotting, immunostaining and DNA/RNA immunoprecipitation-qPCR were conducted to confirm DNA damage and R-loop accumulation in ovarian cancer cells. Co-immunoprecipitation and DNA/RNA immunoprecipitation were performed to detect interaction of DHX9, ADAR1 and R-loop complex in ovarian cancer cells.ResultsWe demonstrated that ADAR1 was highly expressed in ovarian cancer tissues and negatively correlated with progression free survival of ovarian cancer patients. Importantly, silence of ADAR1 repressed ovarian cancer cell growth and colony formation in vitro and inhibited ovarian cancer cell tumorigenesis in vivo. Further cell cycle and transcriptome profile analysis revealed that silence of ADAR1 in ovarian cancer cells induced cell cycle arrest at G1/G0 stage. Mechanically, loss of ADAR1 caused R-loop abnormal accumulation, thereby contributing to single stand DNA break and ATR pathway activation. Additionally, ADAR1 interacted with DHX9 to regulate R-loop complex formation, and A-to-I editing of nascent RNA repressed R-loop formation during co-transcriptional process. ConclusionsOur results identify a novel ADAR1/R-loop/ATR axis critical for ovarian cancer progression and a potential target for ovarian cancer therapy.

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