GATA3 suppresses human fibroblasts-induced metastasis of clear cell renal cell carcinoma via an anti-IL6/STAT3 mechanism

Shi, Qianqian; Xu, Ran; Song, Guanglai; Lü, Hao; Dong, Xue; He, Xiaozhou; Xia, Ying

doi:10.1038/s41417-019-0146-2

Cited by 7 publications

(4 citation statements)

References 57 publications

(60 reference statements)

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“…Therefore, we speculate that FTY720 reduced growth and invasion and encouraged apoptosis of sacrum chordoma cells via inhibition of IL-6/STAT3 signalling [43]. The IL-6/STAT3 pathway has a crucial function in the metastasis of various tumours, such as colorectal cancer and renal cell carcinoma (RCC) [44][45][46].…”

Section: Discussionmentioning

confidence: 99%

Fingolimod inhibits proliferation and epithelial–mesenchymal transition in sacral chordoma by inactivating IL-6/STAT3 signalling

Wang

et al. 2020

Bioscience Reports

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Purpose: To explore the sensitivity of the immunosuppressive agent fingolimod (FTY720) in chordoma and determine whether it can serve as an appropriate alternate treatment for unresectable tumours in patients after incomplete surgery. Methods: Cell viability assays, colony formation assays and EdU assays were performed to evaluate the sensitivity of chordoma cell lines to FTY720. Transwell invasion assays, wound healing assays, flow cytometry, cell cycle analysis, immunofluorescence analysis, Western blotting analysis and enzyme-linked immunosorbent assays (ELISAs) were performed to evaluate cell invasion, epithelial–mesenchymal transition (EMT) and activation of related pathways after treatment with FTY720. The effect of FTY720 was also evaluated in vivo in a xenograft model. Results: We found that FTY720 inhibited the proliferation, invasion and metastasis of sacral chordoma cells (P < 0.01). FTY720 also inhibited the proliferation of tumour cells in a xenograft model using sacral chordoma cell lines (P < 0.01). The mechanism was related to the EMT and apoptosis of chordoma cells and inactivation of IL-6/STAT3 signalling in vitro and in vivo. Conclusions: Our findings indicate that FTY720 may be an effective therapeutic agent against chordoma. These findings suggest that FTY720 is a novel agent that can treat locally advanced and metastatic chordoma.

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Section: Discussionmentioning

confidence: 99%

Fingolimod inhibits proliferation and epithelial–mesenchymal transition in sacral chordoma by inactivating IL-6/STAT3 signalling

Wang

et al. 2020

Bioscience Reports

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“…In addition, the distant metastasis ability of esophageal tumor cells in propofol treatment group was also signi cantly reduced after HU treatment. It is reported that after HU-induced DNA arrest, the replication fork will ip under the action of RPA and RAD51 proteins to form a Holliday junction structure and maintain the stability of the replication fork [24]. If the stagnation factor persists, the replication fork will cause single strand and double strand damage under the action of exonuclease, which will activate ATR signal pathway and promote DNA repair [25].…”

Section: Discussionmentioning

confidence: 99%

Propofol Regulates the Proliferation and Migration of Lung Cancer Cells Through Atr Signaling Pathway

Zhou

Liang

et al. 2022

Preprint

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Aims: Here we aim to investigate the regulation of propofol on DNA damage caused by replication fork arrest in esophageal squamous cell carcinoma cells.Methods: A549 and NCI-H460 cells were treated with propofol and hydroxyurea (HU) in vitro. CCK-8 assay was used to examine cell proliferation. Transwell assay was employed to investigate cell migration and invasion abilities. Western blotting was carried out to study the activities of ATR signals. Laser confocal microscopy was utilized to study the formation of p-RPA32 foci.Results: Propofol treatment promoted the apoptosis and suppresses the proliferation, migration and invasion, possibly by increasing the sensitivity of A549 and NCI-H460 cells against DNA damage. Propofol treatment enhanced the sensitivity of A549 and NCI-H460 cells to damages caused by replication fork arrest, as well as the activity of ATR signaling pathway. Propofol regulated the sensitivity of A549 and NCI-H460 cells to DNA replication damage by affecting the level of H3K27me3.Conclusions: The present study demonstrates that propofol up-regulates the expression of H3K27me3 in lung cancer cells, promotes the recruitment of exonuclease MUS81 in stagnant replication fork, induces apoptosis caused by DNA damage, and thus inhibits the proliferation and metastasis of tumor cells.

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“…Bioinformatics analyses indicated that binding sites for GATA transcription factors were available in the promoter of FMNL1 (data not shown). Previous studies showed that GATA3 was capable of suppressing ccRCC metastasis (13). Interestingly, in GEO studies (no.…”

Section: Fmnl1 Upregulation Is Mediated By the Loss Of Gata3 In Ccrccmentioning

confidence: 97%

FMNL1 Exhibits Pro-Metastatic Activity via CXCR2 in Clear Cell Renal Cell Carcinoma

Zhang

Yang

et al. 2020

Front. Oncol.

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Formin-like (FMNL) proteins are responsible for cytoskeletal remodeling and have been implicated in the progression and spread of human cancers. Yet the clinical significance and biological function of FMNL1 in clear cell renal cell carcinoma (ccRCC) remain unclear. In this study, the expression of FMNL1 in ccRCC and its clinical value were determined by tissue microarray-based IHC and statistical analyses. The role of FMNL1 in ccRCC metastasis and the underlying mechanism were investigated via in vitro and in vivo models using gene regulation detection, ChIP, Luciferase reporter assays, and rescue experiments. We show that FMNL1 is upregulated in ccRCC and exhibits pro-metastatic activity via induction of CXCR2. High expression of FMNL1 is significantly correlated with advanced tumor stage, higher pathological tumor grade, tumor metastasis, and unfavorable prognosis in two independent cohorts containing over 800 patients with ccRCC. The upregulation of FMNL1 in ccRCC is mediated by the loss of GATA3. Ectopic expression of FMNL1 promotes, whereas FMNL1 depletion inhibits cell migration in vitro and tumor metastasis in vivo. The FMNL1-enhanced cell mobility is markedly attenuated by the knockdown of CXCR2. Further studies demonstrate that FMNL1 increases the expression of CXCR2 via HDAC1. In clinical samples, FMNL1 expression is positively associated with CXCR2, and is negatively connected to GATA3 expression. Collectively, our data suggest FMNL1 serve as a potential prognostic factor and function as an oncogene. The axis of GATA3/FMNL1/CXCR2 may present a promising therapeutic target for tumor metastasis in ccRCC.

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GATA3 suppresses human fibroblasts-induced metastasis of clear cell renal cell carcinoma via an anti-IL6/STAT3 mechanism

Cited by 7 publications

References 57 publications

Fingolimod inhibits proliferation and epithelial–mesenchymal transition in sacral chordoma by inactivating IL-6/STAT3 signalling

Fingolimod inhibits proliferation and epithelial–mesenchymal transition in sacral chordoma by inactivating IL-6/STAT3 signalling

Propofol Regulates the Proliferation and Migration of Lung Cancer Cells Through Atr Signaling Pathway

FMNL1 Exhibits Pro-Metastatic Activity via CXCR2 in Clear Cell Renal Cell Carcinoma

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