An integrated analysis identifies STAT4 as a key regulator of ovarian cancer metastasis

Zhao, Linjie; Ji, Gaili; Le, Xiaobing; Luo, Zhangjie; Wang, C; Feng, Min; Xu, Lian; Zhang, Y; Lau, Wayne Bond; Lau, Bonnie; Yang, Yun; Luo, Lei; Yang, Huiliang; Yao, Xuan; Chen, Y; Deng, Xiangbing; Yi, Tao; Yao, Su; Zhao, Xia; Wei, Yuquan; Zhou, Shengtao

doi:10.1038/onc.2016.487

Cited by 81 publications

(68 citation statements)

References 33 publications

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“…9,94 Moreover, tumor-derived Wnt7a induces the generation of cancer-associated fibroblasts-like cells involved in ovarian cancer metastasis. 96 These findings demonstrate that Wnt7a promotes ovarian cancer initiation and progression in an autocrinal and paracrinal manner. In breast cancer, Wnt7a is a target gene of TGF-β and enhances both basal and TGF-β-induced invasion.…”

Section: Tumors (As a Tumor Promoter)mentioning

confidence: 76%

“…Wnt7a promotes ovarian cancer cell growth and invasion in a β‐catenin/TCF‐MMP‐7 dependent manner . Moreover, tumor‐derived Wnt7a induces the generation of cancer‐associated fibroblasts‐like cells involved in ovarian cancer metastasis . These findings demonstrate that Wnt7a promotes ovarian cancer initiation and progression in an autocrinal and paracrinal manner.…”

Section: Roles Of Wnt7a In Human Diseasesmentioning

confidence: 78%

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Roles of Wnt7a in embryo development, tissue homeostasis, and human diseases

Lan

Wang

Huang

et al. 2019

J of Cellular Biochemistry

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Human Wnt family comprises 19 proteins which are critical to embryo development and tissue homeostasis. Binding to different frizzled (FZD) receptor, Wnt7a initiates both β‐catenin dependent pathway, and β‐catenin independent pathways such as PI3K/Akt, RAC/JNK, and extracellular signal‐regulated kinase 5/peroxisome proliferator‐activated receptor‐γ. In the embryo, Wnt7a plays a crucial role in cerebral cortex development, synapse formation, and central nervous system vasculature formation and maintenance. Wnt7a is also involved in the development of limb and female reproductive system. Wnt7a mutation leads to human limb malformations and animal female reproductive system defects. Wnt7a is implicated in homeostasis maintenance of skeletal muscle, cartilage, cornea and hair follicle, and Wnt7a treatment may be potentially applied in skeletal muscle dystrophy, corneal damage, wound repair, and hair follicle regeneration. Wnt7a plays dual roles in human tumors. Wnt7a is downregulated in lung cancers, functioning as a tumor suppressor, however, it is upregulated in several other malignancies such as ovarian cancer, breast cancer, and glioma, acting as a tumor promoter. Moreover, Wnt7a overexpression is associated with inflammation and fibrosis, but its roles need to be further investigated.

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Section: Tumors (As a Tumor Promoter)mentioning

confidence: 76%

Section: Roles Of Wnt7a In Human Diseasesmentioning

confidence: 78%

Roles of Wnt7a in embryo development, tissue homeostasis, and human diseases

Lan

Wang

Huang

et al. 2019

J of Cellular Biochemistry

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“…STAT1-mediated pentraxin3 secretion in fibroblasts promotes cell proliferation in breast cancer [27]. Unlike other STAT proteins (for example, STAT1, STAT2 and STAT3), which appear to be widely expressed in a variety of cancer tissues, STAT4 has recently emerged in a few tumor types, including gastric cancer, ovarian cancer, colorectal cancer and lymphoma [7][8][9]30].…”

Section: Discussionmentioning

confidence: 99%

miR-200a-3p predicts prognosis and inhibits bladder cancer cell proliferation by targeting STAT4

et al. 2019

Arch Med Sci

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Introduction: STAT4 is a transcriptional regulator that has been reported to have oncogenic activities in various cancers. In our study, the posttranscriptional regulatory effect of miR-200a-3p on STAT4 and the prognostic significance of miR-200a-3p and STAT4 were evaluated in bladder cancer (BCa). Material and methods: Proliferation and apoptosis of BCa cell lines were monitored using CCK-8 and Annexin V-FITC assays, respectively. Gene and protein expression levels in BCa tissues and cells were detected using RT-qP-CR and western blotting, respectively. Results: Significant downregulation of miR-200a-3p and upregulation of STAT4 were observed in BCa tissues and cells compared with the corresponding non-tumor adjacent tissues. Both STAT4 and miR-200a-3p were validated as independent prognostic indicators in sixty-nine BCa patients for predicting overall survival and disease-free survival. In vitro experimental analyses revealed that knockdown of STAT4 repressed BCa cell growth and elevated cell apoptosis. Molecular interactive analysis revealed STAT4 as a direct target of miR-200a-3p, which could suppress STAT4 protein expression by posttranscriptional repression. Cotransfection of miR-200a-3p mimics and STAT4 overexpression plasmids into BCa cells demonstrated that the antineoplastic activities of miR-200a-3p in vitro were neutralized by overexpressed STAT4. Conclusions: The miR-200a-3p/STAT4 signaling cascade plays an important role in the progression of BCa, which provides a new promising target for targeted BCa therapies.

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“…Overexpression of STAT4 has been found in epithelial cells of OC and with poor prognosis of patients. STAT4 mediates the EMT process via cancer-stroma interactions, and promotes metastasis via cancer-associated fibroblasts induced by Wnt7a [139].…”

Section: Other Diseasesmentioning

confidence: 99%

STAT4: an immunoregulator contributing to diverse human diseases

Yang¹,

Mai²,

Peng³

et al. 2020

Int. J. Biol. Sci.

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Signal transducer and activator of transcription 4 (STAT4) is a member of the STAT family and localizes to the cytoplasm. STAT4 is phosphorylated after a variety of cytokines bind to the membrane, and then dimerized STAT4 translocates to the nucleus to regulate gene expression. We reviewed the essential role played by STAT4 in a wide variety of cells and the pathogenesis of diverse human diseases, especially many kinds of autoimmune and inflammatory diseases, via activation by different cytokines through the Janus kinase (JAK)-STAT signaling pathway.

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An integrated analysis identifies STAT4 as a key regulator of ovarian cancer metastasis

Cited by 81 publications

References 33 publications

Roles of Wnt7a in embryo development, tissue homeostasis, and human diseases

Roles of Wnt7a in embryo development, tissue homeostasis, and human diseases

miR-200a-3p predicts prognosis and inhibits bladder cancer cell proliferation by targeting STAT4

STAT4: an immunoregulator contributing to diverse human diseases

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