Sox5 contributes to prostate cancer metastasis and is a master regulator of TGF-β-induced epithelial mesenchymal transition through controlling Twist1 expression

Hu, Jielun; Tian, Jing; Zhu, Shimiao; Sun, Lili; Yu, Jianpeng; Tian, Haijun; Dong, Qian; Luo, Qiang; Jiang, Ning; Niu, Yuanjie; Shang, Zhiqun

doi:10.1038/bjc.2017.372

Cited by 57 publications

(44 citation statements)

References 33 publications

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“…SOX5 is a member of the SOX family of transcription factors and plays a critical role in the progression of various cancer types. It has been reported that SOX5 may regulate epithelial-mesenchymal transition (EMT) via altering the expression of the twist-related protein 1 (Twist1) and, consequently, facilitating metastasis in prostate cancer [40]. Besides, it has been found that SOX5 overexpression may reverse apoptosis induced by miR-132 and miR-15a/16 in pituitary tumor cells and that SOX5 is upregulated in invasive pituitary tumor tissues [41].…”

Section: Discussionmentioning

confidence: 99%

Apatinib inhibits glycolysis by suppressing the VEGFR2/AKT1/SOX5/GLUT4 signaling pathway in ovarian cancer cells

Chen

Cheng

et al. 2019

Cell Oncol.

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Background Apatinib is a tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor-2 (VEGFR2), and has shown encouraging therapeutic effects in various malignant tumors. As yet, however, the role of apatinib in ovarian cancer has remained unknown. Here, we sought to elucidate the role of apatinib in the in vitro and in vivo viability and proliferation of ovarian cancer cells, as well as in glucose metabolism in these cells. Methods The effects of apatinib on ovarian cancer cell viability and proliferation were assessed using Cell Counting Kit-8 (CCK-8) and colony formation assays, respectively. The expression of VEGFR2/AKT1/SOX5/GLUT4 pathway proteins was assessed using Western blotting, and glucose uptake and lactate production assays were used to detect glycolysis in ovarian cancer cells. SOX5 was exogenously over-expressed and silenced in ovarian cancer cells using expression vector and shRNA-based methods, respectively. RNA expression analyses were performed using RNA-seq and gene-chip-based methods. GLUT4 promoter activity was assessed using a dual-luciferase reporter assay. The expression of p-VEGFR2 (Tyr1175), p-AKT1 (Ser473), p-GSK3β (Ser9), SOX5 and GLUT4 in xenograft tissues was assessed using immunohistochemistry (IHC). Results We found that apatinib inhibited the in vitro and in vivo viability and proliferation in Hey and OVCA433 ovarian cancer cells in a dose-dependent and time-dependent manner. We also found that apatinib effectively suppressed glucose uptake and lactate production by blocking the expression of GLUT4 in these cells. In addition, we found that SOX5 predominantly rescued the inhibitory effect of apatinib on GLUT4 expression by activating its promoter. Finally, we found that apatinib regulated the expression of SOX5 by suppressing the VEGFR2/AKT1/GSK3β signaling pathway. Conclusions From our results, we conclude that apatinib suppresses the in vitro and in vivo viability and proliferation of ovarian cancer cells, as well as glycolysis by inhibiting the VEGFR2/AKT1/GSK3β/SOX5/GLUT4 signaling pathway. Apatinib may serve as a promising drug for the treatment of ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

Apatinib inhibits glycolysis by suppressing the VEGFR2/AKT1/SOX5/GLUT4 signaling pathway in ovarian cancer cells

Chen

Cheng

et al. 2019

Cell Oncol.

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“…After the secondary antibody was added dropwise, it was incubated at room temperature for 1 h, and after washing with PBS, the nuclei were stained with DAPI. The photograph was taken under an Olympus FV1000D confocal microscope [18].…”

Section: Immunofluorescence Stainingmentioning

confidence: 99%

“…The prepared cells were subjected to the YAP1 or TEAD1 CHIP assay using the EpiQuik Chromatin Immunoprecipitation Kit (Epigentek, Farmingdale, NY, USA) according to the protocol [18]. PCR was performed using primers specific for the YAP1 or TEAD1 binding regions in the SRC promoter.…”

Section: Chromatin Immunoprecipitation (Chip)mentioning

confidence: 99%

YAP1 plays a key role of the conversion of normal fibroblasts into cancer-associated fibroblasts that contribute to prostate cancer progression

Shen

Yang

Zhu

et al. 2020

J Exp Clin Cancer Res

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Background: Cancer-associated fibroblasts (CAFs) are an important part of the tumour microenvironment, and their functions are of great concern. This series of experiments aimed to explore how Yes-associated protein 1 (YAP1) regulates the function of stromal cells and how the normal fibroblasts (NFs) convert into CAFs in prostate cancer (PCa). Methods: The effects of conditioned media from different fibroblasts on the proliferation and invasion of epithelial cells TrampC1 were examined. We then analysed the interaction between the YAP1/TEAD1 protein complex and SRC, as well as the regulatory function of the downstream cytoskeletal proteins and actins. A transplanted tumour model was used to explore the function of YAP1 in regulating tumour growth through stromal cells. The relationship between the expression of YAP1 in tumour stromal cells and the clinical characteristics of PCa patients was analysed. Results: The expression level of YAP1 was significantly upregulated in PCa stromal cells. After the expression level of YAP1 was increased, NF was transformed into CAF, enhancing the proliferation and invasion ability of epithelial cells. The YAP1/TEAD1 protein complex had the capability to influence downstream cytoskeletal proteins by regulating SRC transcription; therefore, it converts NF to CAF, and CAF can significantly promote tumour growth and metastasis. The high expression of YAP1 in the tumour stromal cells suggested a poor tumour stage and prognosis in PCa patients. Conclusion: YAP1 can convert NFs into CAFs in the tumour microenvironment of PCa, thus promoting the development and metastasis of PCa. Silencing YAP1 in tumour stromal cells can effectively inhibit tumour growth.

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“…There is evidence that creBBP is downregulated in Pca and is a tumor suppressor gene in small-cell lung cancer and other neuroendocrine tumors (63,64). Smad3/Sox5/Twist1 was reported to promote eMT and cancer progression in Pca (65). Mcc, a candidate tumor suppressor gene, was revealed to be often silenced by hypermethylation of its promoter in colorectal cancer (66).…”

Section: Discussionmentioning

confidence: 99%

Identification of aberrantly methylated‑differentially expressed genes and gene ontology in prostate cancer

Wang

Wang²,

Quan

2019

Mol Med Report

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Prostate cancer (Pca) is the most frequent urological malignancy in men worldwide. dna methylation has an essential role in the etiology and pathogenesis of Pca. The purpose of the present study was to identify the aberrantly methylated-differentially expressed genes and to determine their potential roles in Pca. The important node genes identified were screened by integrated analysis. Gene expression microarrays and gene methylation microarrays were downloaded and aberrantly methylated-differentially expressed genes were obtained. enrichment analysis and protein-protein interactions (PPi) were obtained, their interactive and visual networks were created, and the node genes in the PPi network were validated. a total of 105 hypomethylation-high expression genes and 561 hypermethylation-low expression genes along with their biological processes were identified. The top 10 node genes obtained from the PPI network were identified for each of the two gene groups. The methylation and gene expression status of node genes in TCGA database, GEPIA tool, and the HPa database were generally consistent with those of our results. In conclusion, the present study identified 20 aberrantly methylated-differentially expressed genes in Pca by combining bioinformatics analyses of gene expression and gene methylation microarrays, and concurrently, the survival of these genes was analyzed. notably, methylation is a reversible biological process, which makes it of great biological significance for the diagnosis and treatment of prostate cancer using bioinformatics technology to determine abnormal methylation gene markers. The present study provided novel therapeutic targets for the treatment of Pca.

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Sox5 contributes to prostate cancer metastasis and is a master regulator of TGF-β-induced epithelial mesenchymal transition through controlling Twist1 expression

Abstract: Therefore, we propose a new mechanism in which Smad3/Sox5/Twist1 promotes EMT and contributes to PCa progression.

Cited by 57 publications

References 33 publications

Apatinib inhibits glycolysis by suppressing the VEGFR2/AKT1/SOX5/GLUT4 signaling pathway in ovarian cancer cells

Apatinib inhibits glycolysis by suppressing the VEGFR2/AKT1/SOX5/GLUT4 signaling pathway in ovarian cancer cells

YAP1 plays a key role of the conversion of normal fibroblasts into cancer-associated fibroblasts that contribute to prostate cancer progression

Identification of aberrantly methylated‑differentially expressed genes and gene ontology in prostate cancer

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