scholarly journals FoxM1 affects adhesive, migratory, and invasive abilities of human retinoblastoma Y-79 cells by targeting matrix metalloproteinase 2

2020 ◽  
Vol 52 (3) ◽  
pp. 294-301
Author(s):  
Xue Zhu ◽  
Mengxi Yu ◽  
Ke Wang ◽  
Wenjun Zou ◽  
Ling Zhu
Keyword(s):  
Matrix Metalloproteinase ◽  
Tumor Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Matrix Metalloproteinase 2 ◽  
Luciferase Reporter ◽  
Mesenchymal Transition ◽  
Forkhead Box ◽  
Cell Metastasis ◽  
Human Retinoblastoma ◽  
Novel Target

Abstract Forkhead box protein M1 (FoxM1) is an important transcription factor involved in various pathological processes including tumor metastasis. The changes of adhesive, migratory, and invasive abilities are considered as crucial events in tumor metastasis progression. In this study, we aimed to investigate the correlation between FoxM1 and retinoblastoma (Rb) metastasis and to explore the detailed mechanism. Wound healing, cell adhesion, and invasion assays showed that FoxM1 overexpression induced epithelial–mesenchymal transition in Y-79 cells and inhibited adhesion and subsequently promoted metastasis of Y-79 cells, while FoxM1 knockdown showed the opposite effects. A luciferase reporter assay and chromatin immunoprecipitation assay provided evidence that FoxM1 promoted matrix metalloproteinase 2 (MMP2) transcription by directly binding to and promoting MMP2 promoter. MMP2 knockdown by siRNA transfection attenuated cell metastasis of Y-79 cells induced by FoxM1 overexpression. Furthermore, the FoxM1-binding site mapped between −1167 and −1161 bp of the MMP2 promoter was identified. Our results suggested that the FoxM1–MMP2 axis plays an important role in Rb metastasis, which may be a novel target for designing therapeutic regimen to control Rb metastasis.

scholarly journals Effect of PACAP on Hypoxia-Induced Angiogenesis and Epithelial–Mesenchymal Transition in Glioblastoma

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 965
Author(s):  
Grazia Maugeri ◽  
Agata Grazia D’Amico ◽  
Salvatore Saccone ◽  
Concetta Federico ◽  
Daniela Maria Rasà ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Matrix Metalloproteinase 2 ◽  
Mesenchymal Transition ◽  
Hypoxic Area ◽  
Vitro Model ◽  
Human Gbm ◽  
Endothelial Growth Factor

Pituitary adenylate cyclase-activating polypeptide (PACAP) exerts different effects in various human cancer. In glioblastoma (GBM), PACAP has been shown to interfere with the hypoxic micro-environment through the modulation of hypoxia-inducible factors via PI3K/AKT and MAPK/ERK pathways inhibition. Considering that hypoxic tumor micro-environment is strictly linked to angiogenesis and Epithelial–Mesenchymal transition (EMT), in the present study, we have investigated the ability of PACAP to regulate these events. Results have demonstrated that PACAP and its related receptor, PAC1R, are expressed in hypoxic area of human GBM colocalizing either in epithelial or mesenchymal cells. By using an in vitro model of GBM cells, we have observed that PACAP interferes with hypoxic/angiogenic pathway by reducing vascular-endothelial growth factor (VEGF) release and inhibiting formation of vessel-like structures in H5V endothelial cells cultured with GBM-conditioned medium. Moreover, PACAP treatment decreased the expression of mesenchymal markers such as vimentin, matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) as well as CD44 in GBM cells by affecting their invasiveness. In conclusion, our study provides new insights regarding the multimodal role of PACAP in GBM malignancy.

Pomegranate extract inhibits migration and invasion of oral cancer cells by downregulating matrix metalloproteinase‐2/9 and epithelial‐mesenchymal transition

2020 ◽  
Vol 35 (6) ◽  
pp. 673-682 ◽  
Author(s):  
Sheng‐Yao Peng ◽  
Chien‐Chou Hsiao ◽  
Ting‐Hsun Lan ◽  
Ching‐Yui Yen ◽  
Ammad A. Farooqi ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Matrix Metalloproteinase ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Matrix Metalloproteinase 2 ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Oral Cancer Cells

Matrix metalloproteinase 2 induces epithelial-mesenchymal transition in proximal tubules from the luminal side and progresses fibrosis in mineralocorticoid/salt-induced hypertensive rats

2011 ◽  
Vol 29 (12) ◽  
pp. 2440-2453 ◽  
Author(s):  
Yoshitaka Iwazu ◽  
Shigeaki Muto ◽  
Ichiro Hirahara ◽  
Genro Fujisawa ◽  
Shin-ichi Takeda ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Epithelial Mesenchymal Transition ◽  
Proximal Tubules ◽  
Matrix Metalloproteinase 2 ◽  
Hypertensive Rats ◽  
Mesenchymal Transition ◽  
Luminal Side

scholarly journals Osteopontin Promotes Invasion, Migration and Epithelial-Mesenchymal Transition of Human Endometrial Carcinoma Cell HEC-1A Through AKT and ERK1/2 Signaling

2015 ◽  
Vol 37 (4) ◽  
pp. 1503-1512 ◽  
Author(s):  
Yinghua Li ◽  
Yunpeng Xie ◽  
Dan Cui ◽  
Yanni Ma ◽  
Linlin Sui ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Cell Counting ◽  
Matrix Metalloproteinase 2 ◽  
Migration And Invasion ◽  
Related Factors ◽  
Western Blots ◽  
Mesenchymal Transition ◽  
Novel Target

Background/Aims: Osteopontin (OPN) is an Extracellular Matrix (ECM) molecule and is involved in many physiologic and pathologic processes, including cell adhesion, angiogenesis and tumor metastasis. OPN is a well-known multifunctional factor involved in various aspects of cancer progression, including endometrial cancer. In this study, we examined the significance of OPN in endometrial cancer. Methods: The proliferation, migration and invasion ability of HEC-1A cells were detected by Cell Counting Kit-8 (CCK-8), Wound scratch assay and transwell. Western blots were employed to detect the expression of Matrix metalloproteinase-2 (MMP-2) and epithelial-mesenchymal transition (EMT)-related factors in HEC-1A cells treated with rhOPN. Results: rhOPN promotes cell proliferation, migration and invasion in HEC-1A cells. rhOPN influenced EMT-related factors and MMP-2 expression in HEC-1A cells. rhOPN promoted HEC-1A cells migration, invasion and EMT through protein kinase B (PKB/AKT) and Extracellular regulated protein kinases (ERK1/2) signaling pathway. Conclusions: These results may open up a novel therapeutic strategy for endometrial cancer: namely, rhOPN have important roles in controlling growth of endometrial of cancer cells and suggest a novel target pathway for treatment of this cancer.

MiR-196a promoted cell migration, invasion and the epithelial-mesenchymal transition by targeting HOXA5 in osteosarcoma

2020 ◽  
Vol 29 (2) ◽  
pp. 291-298
Author(s):  
Xiaoli Wang ◽  
Lili Zhang ◽  
Xingfeng Zhang ◽  
Cuihong Xing ◽  
Ruidong Liu ◽  
...  
Keyword(s):  
Cell Migration ◽  
Epithelial Mesenchymal Transition ◽  
Bone Cancer ◽  
Luciferase Reporter ◽  
Mesenchymal Transition ◽  
Tumor Tissues ◽  
Cell Metastasis ◽  
Primary Bone ◽  
Polymerase Chain ◽  
Dual Luciferase Reporter Assay

INTRODUCTION: Osteosarcoma (OS), aggressive neoplasms of the bone, is the most common primary bone cancer in children. MiR-196a usually low expressed in several tumors and its functions in osteosarcoma still unclear. MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to assess the expression of miR-196a and the HOXA5. Cell metastasis and epithelial-mesenchymal transition (EMT) abilities were assessed using Transwell and western blot. The dual luciferase reporter assay was carried out to verify whether miR-196a directly targeted the 3’-untranslated region (UTR) of HOXA5 mRNA. RESULTS: MiR-196a was overexpressed and HOXA5 was low expressed in osteosarcoma versus the non-tumor tissues and normal cell lines. Upregulation of miR-196a or downregulation of HOXA5 was associated with worse outcome of osteosarcoma patients. MiR-196a enhanced cell migration, invasion and EMT by regulating the expression of HOXA5 through directly targeting the 3’-UTR of its mRNA in osteosarcoma. HOXA5 partially reversed roles of miR-196a on metastasis and EMT in osteosarcoma. CONCLUSIONS: MiR-196a promoted cell metastasis and EMT by targeting the 3’-UTR of HOXA5 mRNA in osteosarcoma. The newly identified miR-196a/HOXA5 axis provides novel insight into the pathogenesis of osteosarcoma.

miR-345 inhibits migration and stem-like cell phenotype in gastric cancer via inactivation of Rac1 by targeting EPS8

2020 ◽  
Vol 52 (3) ◽  
pp. 259-267
Author(s):  
Jieyun Zhang ◽  
Chenchen Wang ◽  
Shican Yan ◽  
Yanan Yang ◽  
Xiaowei Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Lines ◽  
Tumor Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Growth Factor Receptor ◽  
Luciferase Reporter ◽  
Cell Phenotype ◽  
Spheroid Formation ◽  
Mesenchymal Transition ◽  
Mirna Array

Abstract Tumor metastasis is the main cause of treatment failure and death in patients with late stage of gastric cancer (GC). Studies showed that microRNAs (miRNAs) are important regulators in the process of tumor metastasis. In this study, we used miRNA array analysis to search for metastasis-associated miRNAs in primary and matched metastasis tissues of patients with GC and found that miR-345-5p (miR-345) was significantly higher in primary sites. Decreased expression of miR-345 was observed in GC tissues and cell lines, which was correlated with aggressive stage and grade. Patients with a higher level of miR-345 had a better prognosis. miR-345 could inhibit the migration and spheroid formation abilities in GC cell lines in transwell assay and spheroid formation assay. RNA sequencing and bioinformatics analysis revealed that miR-345 downregulated the epidermal growth factor receptor pathway substrate 8 (EPS8) and its downstream Rac1 signaling. Mechanistically, we confirmed that miR-345 could target EPS8 by directly binding to its 3′ untranslated region by luciferase reporter assay. Further rescue assay showed that the ability of miR-345 in inhibiting the migration, stem-like cell phenotype, and epithelial–mesenchymal transition (EMT) in GC was partly dependent on targeting EPS8. In conclusion, miR-345 plays an inhibitory role in GC metastasis through inhibiting cell migration, EMT, and cancer stem cell phenotype via inactivation of Rac1 signaling by targeting EPS8, which provides the potential therapeutic and predictive value of miR-345 in GC.

Sign in / Sign up

Export Citation Format

Share Document