scholarly journals Fisetin Suppresses the Proliferation and Metastasis of Renal Cell Carcinoma through Upregulation of MEK/ERK-Targeting CTSS and ADAM9

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 948 ◽  
Author(s):  
Hsieh ◽  
Tsai ◽  
Yang ◽  
Chiou ◽  
Lin ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Renal Cell Carcinoma ◽  
Cell Migration ◽  
Cell Viability ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Renal Cell ◽  
Mapk Signaling ◽  
Migration And Invasion ◽  
Proliferation And Metastasis

Fisetin, a natural flavonoid, is known to have anticarcinogenic effects against several cancers, but its role in mediating renal cell carcinoma (RCC) progression has not been delineated. Cell viability, cytotoxicity, and cell cycle distribution were measured using the 3‐(4,5‐cimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide assay and propidium iodide staining with flow cytometry. The in vitro migration and invasion assay was used to examine in vivo cell migration and invasion. Human protease antibody array analysis was conducted with cell migration/invasion-related proteins. Western blotting and quantitative reverse transcription polymerase chain reaction were used for assessing protein expression related to the cell cycle, cell invasion, and mitogen-activated protein kinase (MAPK) signaling pathway. We found that fisetin significantly inhibited cell viability through cell cycle arrest in the G2/M phase, in addition to downregulating cyclin D1 and upregulating p21/p27. Fisetin inhibited the migration and invasion of human RCC cells through the downregulation of CTSS and a disintegrin and metalloproteinase 9 (ADAM9). Fisetin also upregulated ERK phosphorylation in 786-O and Caki-1 cells. Furthermore, treatment with a MEK inhibitor (UO126) reduced the inhibitory effects of fisetin on the metastasis of RCC cells through the ERK/CTSS/ADAM9 pathway. Fisetin inhibits proliferation and metastasis of RCC cells by downregulating CTSS and ADAM9 through the MEK/ERK signaling pathway. These findings indicate that fisetin is a promising antitumor agent against RCC.

scholarly journals Ampelopsin Inhibits Cell Viability and Metastasis in Renal Cell Carcinoma by Negatively Regulating the PI3K/AKT Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Zhonghe Zhao ◽  
Yan Jiang ◽  
Zhongguo Liu ◽  
Qingyan Li ◽  
Tiantian Gao ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Migration ◽  
Cell Viability ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Renal Cell ◽  
Inhibitory Effect ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Akt Signaling Pathway

Background. Previous studies have shown that Ampelopsin has an inhibitory effect on human tumors. However, the effect of Ampelopsin on renal cell carcinoma (RCC) is rarely reported. Therefore, this study aims to explain the role of Ampelopsin in RCC. Methods. Different concentrations of Ampelopsin (0, 10, 25, 50, and 100 μM) were used to treat 786-O cells. Cell viability was detected by MTT assay, colony formation assay, and flow cytometry assay. Transwell assay and Wound healing assay were used to detect cell migration and invasion. Western blot analysis was applied to detect protein expression. Results. Ampelopsin inhibited cell proliferation and induced apoptosis in RCC. And Ampelopsin can inhibit cell migration and invasion in RCC. All these results changed in a dose-dependent manner. Ampelopsin (100 uM) had the strongest inhibitory effect on cell viability and metastasis. In addition, Ampelopsin negatively regulated the PI3K/AKT signaling pathway in RCC cells. Moreover, Ampelopsin was only cytotoxic to RCC cells. Conclusion. Ampelopsin inhibits cell viability and metastasis in RCC by negatively regulating the PI3K/AKT signaling pathway.

scholarly journals Elevated MTA1 induced the migration and invasion of renal cell carcinoma through the NF-κB pathway

BMC Urology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Cai Lv ◽  
Yuan Huang ◽  
Qingqing Lei ◽  
Zhenxiang Liu ◽  
Shixing Shen ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Migration ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Normal Tissue ◽  
Negative Control ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Interfering Rna ◽  
E Cadherin

Abstract Background The metastasis-associated gene 1 (MTA1) has been extensively reported as a crucial oncogene, and its abnormal expression has been associated with the progression of numerous cancers. However, the role of MTA1 in renal cell carcinoma (RCC) progression and metastasis remains unclear. Herein, we investigated the expression of MTA1 and its role in RCC. Methods 109 matched clear cell RCCs (ccRCCs) and corresponding normal tissue samples were analyzed via immunohistochemistry to test the expression of MTA1. Human A498 cell lines were transfected with pcDNA3.1-Flag (control) or Flag-MTA1 to overexpress MTA1 or with specific interfering RNA (si-MTA1) or specific interfering negative control to knockdown MTA1 expression. Transfected cells were used in wound healing and transwell invasion assay. Quantitative real time polymerase chain reaction was used to assess the effect of MTA1 on MMP2/MMP9 and E-cadherin gene expression. Western blot was used to qualify the phosphorylation of p65. Results Herein, we found a significantly increased expression of MTA1 in 109 ccRCCs, compared to the corresponding normal tissue. In addition, the overexpression of MTA1 in A498 cells facilitated cell migration and invasion, while the down-regulation of MTA1 expression using specific interfering RNA sequences could decrease cell migration and invasion. Furthermore, we showed that MTA1 is up-regulated in ccRCCs, which contributes to the migration and invasion of human kidney cancer cells by mediating the expression of MMP2 and MMP9 through the NF-κB signaling pathway. Similarly, we found that MTA1 could regulate E-cadherin expression in RCCs. Conclusions MTA1 is overexpressed in RCC and is involved in the progression of RCC through NF-κB.

scholarly journals Upregulated circPDK1 Promotes RCC Cell Migration and Invasion by Regulating the miR-377-3P-NOTCH1 Axis in Renal Cell Carcinoma

2020 ◽  
Vol Volume 13 ◽  
pp. 11237-11252
Author(s):  
Zhenlin Huang ◽  
Yinghui Ding ◽  
Lu Zhang ◽  
Siyuan He ◽  
Zhankui Jia ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Migration ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Migration And Invasion ◽  
Cell Migration And Invasion

scholarly journals The RabGEF ALS2 is a hypoxia inducible target associated with the acquisition of aggressive traits in tumor cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Solange Rivas ◽  
Patricio Silva ◽  
Montserrat Reyes ◽  
Hugo Sepúlveda ◽  
Luis Solano ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Migration ◽  
Tumor Cell ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Proximal Promoter ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Tumor Cell Migration ◽  
Rab Protein

AbstractTumor hypoxia and the hypoxia inducible factor-1, HIF-1, play critical roles in cancer progression and metastasis. We previously showed that hypoxia activates the endosomal GTPase Rab5, leading to tumor cell migration and invasion, and that these events do not involve changes in Rab protein expression, suggesting the participation of intermediate activators. Here, we identified ALS2, a guanine nucleotide exchange factor that is upregulated in cancer, as responsible for increased Rab5-GTP loading, cell migration and metastasis in hypoxia. Specifically, hypoxia augmented ALS2 mRNA and protein levels, and these events involved HIF-1α-dependent transcription, as shown by RNAi, pharmacological inhibition, chromatin immunoprecipitation and bioinformatics analyses, which identified a functional HIF-1α-binding site in the proximal promoter region of ALS2. Moreover, ALS2 and Rab5 activity were elevated both in a model of endogenous HIF-1α stabilization (renal cell carcinoma) and by following expression of stable non-hydroxylatable HIF-1α. Strikingly, ALS2 upregulation in hypoxia was required for Rab5 activation, tumor cell migration and invasion, as well as experimental metastasis in C57BL/6 mice. Finally, immunohistochemical analyses in patient biopsies with renal cell carcinoma showed that elevated HIF-1α correlates with increased ALS2 expression. Hence, this study identifies ALS2 as a novel hypoxia-inducible gene associated with tumor progression and metastasis.

scholarly journals Tumor suppressive microRNA-138 contributes to cell migration and invasion through its targeting of vimentin in renal cell carcinoma

2012 ◽  
Vol 41 (3) ◽  
pp. 805-817 ◽  
Author(s):  
TAKESHI YAMASAKI ◽  
NAOHIKO SEKI ◽  
YASUTOSHI YAMADA ◽  
HIROFUMI YOSHINO ◽  
HIDEO HIDAKA ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Migration ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Migration And Invasion ◽  
Cell Migration And Invasion

scholarly journals Tumour-suppressivemicroRNA-29sdirectly regulateLOXL2expression and inhibit cancer cell migration and invasion in renal cell carcinoma

FEBS Letters ◽  
2015 ◽  
Vol 589 (16) ◽  
pp. 2136-2145 ◽  
Author(s):  
Rika Nishikawa ◽  
Takeshi Chiyomaru ◽  
Hideki Enokida ◽  
Satoru Inoguchi ◽  
Tomoaki Ishihara ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Migration ◽  
Cell Carcinoma ◽  
Cancer Cell ◽  
Renal Cell ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Cell Migration And Invasion

scholarly journals Long Non-Coding RNA LUCAT1 Promotes Proliferation and Invasion in Clear Cell Renal Cell Carcinoma Through AKT/GSK-3β Signaling Pathway

2018 ◽  
Vol 48 (3) ◽  
pp. 891-904 ◽  
Author(s):  
Zaosong Zheng ◽  
Fengjin Zhao ◽  
Dingjun Zhu ◽  
Jinli Han ◽  
Haicheng Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Migration And Invasion ◽  
Cell Renal Cell Carcinoma ◽  
Normal Tissues ◽  
Gsk 3Β ◽  
Proliferation And Invasion

Background/Aims: Long non-coding RNAs (lncRNAs) have emerged as new regulators and biomarkers in several cancers. However, few lncRNAs have been well characterized in clear cell renal cell carcinoma (ccRCC). Methods: We investigated the lncRNA expression profile by microarray analysis in 5 corresponding ccRCC tissues and adjacent normal tissues. Lung cancer–associated transcript 1 (LUCAT1) expression was examined in 90 paired ccRCC tissues by real-time PCR and validated by The Cancer Genome Atlas (TCGA) database. Kaplan-Meier analysis was used to examine the prognostic value of LUCAT1 and CXCL2 in ccRCC patients. Loss and gain of function were performed to explore the effect of LUCAT1 on proliferation and invasion in ccRCC cells. Western blotting was performed to evaluate the underlying mechanisms of LUCAT1 in ccRCC progression. Chemokine stimulation assay was performed to investigate possible mechanisms controlling LUCAT1 expression in ccRCC cells. Enzyme-linked immunosorbent assays were performed to determine serum CXCL2 in ccRCC patients and healthy volunteers. Receiver operating characteristic curve analysis was performed to examine the clinical diagnostic value of serum CXCL2 in ccRCC. Results: We found that LUCAT1 was significantly upregulated in both clinical ccRCC tissues (n = 90) and TCGA ccRCC tissues (n = 448) compared with normal tissues. Statistical analysis revealed that the LUCAT1 expression level positively correlated with tumor T stage (P < 0.01), M stage (P < 0.01), and TNM stage (P < 0.01). Overall survival and disease-free survival time were significantly shorter in the high-LUCAT1-expression group than in the low-LUCAT1-expression group (log-rank P < 0.01). LUCAT1 knockdown inhibited ccRCC cell proliferation and colony formation, induced cell cycle arrest at G1 phase, and inhibited cell migration and invasion. Overexpression of LUCAT1 promoted proliferation, migration, and invasion of ccRCC cells. Mechanistic investigations showed that LUCAT1 induced cell cycle G1 arrest by regulating the expression of cyclin D1, cyclin-dependent kinase 4, and phosphorylated retinoblastoma transcriptional corepressor 1. Moreover, LUCAT1 promoted proliferation and invasion in ccRCC cells partly through inducing the phosphorylation of AKT and suppressing the phosphorylation of GSK-3β. We also revealed that chemokine CXCL2, upregulated in ccRCC, induced LUCAT1 expression and might be a diagnostic and prognostic biomarker in ccRCC. Conclusions: LUCAT1 was upregulated in ccRCC tissues and renal cancer cell lines, and significantly correlated with malignant stage and poor prognosis in ccRCC. LUCAT1 promoted proliferation and invasion in ccRCC cells through the AKT/GSK-3β signaling pathway. We also revealed that LUCAT1 overexpression was induced by chemokine CXCL2. These findings indicate that the CXCL2/LUCAT1/AKT/GSK-3β axis is a potential therapeutic target and molecular biomarker for ccRCC.

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