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Your search keyword '"Wang, Yujia"' showing total 2 results
2 results on '"Wang, Yujia"'

1. Epiregulin reprograms cancer-associated fibroblasts and facilitates oral squamous cell carcinoma invasion via JAK2-STAT3 pathway.

Author

Wang Y, Jing Y, Ding L, Zhang X, Song Y, Chen S, Zhao X, Huang X, Pu Y, Wang Z, Ni Y, and Hu Q

Subjects
Animals, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell mortality, Carcinoma, Squamous Cell pathology, Cell Line, Tumor, Epiregulin genetics, Female, Fibroblasts metabolism, Gene Expression Regulation, Neoplastic, Humans, Janus Kinase 2 metabolism, Male, Mice, Mice, Inbred BALB C, Mice, Nude, Middle Aged, Mouth Neoplasms genetics, Mouth Neoplasms mortality, Mouth Neoplasms pathology, Neoplasm Invasiveness, STAT3 Transcription Factor metabolism, Signal Transduction, Xenograft Model Antitumor Assays, Cancer-Associated Fibroblasts metabolism, Carcinoma, Squamous Cell metabolism, Epiregulin metabolism, Epithelial-Mesenchymal Transition, Mouth Neoplasms metabolism
Abstract

Background: Local resident normal fibroblasts (NFs) are the major source of cancer-associated fibroblasts (CAFs), which are distinguishable from NFs by their tumor-supportive properties. However, the mechanism and the effects underlying the transition of NFs to CAFs in oral squamous cell carcinoma (OSCC) remain unclear., Methods: Five pairs of matching primary NFs and CAFs derived from OSCC patients were sent for RNA sequencing. Epiregulin (EREG) expression was analyzed by IHC in fibroblasts from OSCC patients. The role of EREG in the NF-CAF transition and the consequential effects on OSCC progression were examined by upregulation/downregulation of EREG in NFs/CAFs both in vitro and in vivo., Results: Here, we identified epiregulin (EREG) as the most remarkably upregulated gene in CAFs. High EREG expression in CAFs correlated with higher T stage, deeper invasion and inferior worst pattern of invasion (WPOI) in OSCC patients and predicted shorter overall survival. Overexpression of EREG in NFs activated the CAF phenotype. Mechanistically, the JAK2/STAT3 pathway was enhanced by EREG in parallel with increased IL-6 expression, which could be inhibited by the JAK2 inhibitor AG490. Recombinant IL-6 upregulated the JAK2/STAT3/EREG pathway in a feedback loop. Moreover, EREG-induced CAF activation promoted the epithelial-mesenchymal transition (EMT) necessary for migration and invasion, which was dependent on JAK2/STAT3 signaling and IL-6. In vivo, EREG expression in stroma fibroblasts promoted tumor growth with high stromal α-SMA, phospho-JAK2/STAT3, and IL-6 expression and upregulated EMT in HSC3 cells., Conclusions: EREG is essential for the NF-CAF transformation needed to induce EMT of tumor cells in a JAK2-STAT3- and IL-6-dependent manner in OSCC.

Published
2019
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2. Epiregulin reprograms cancer-associated fibroblasts and facilitates oral squamous cell carcinoma invasion via JAK2-STAT3 pathway

Author

Yanhong Ni, Xiaofeng Huang, Sheng Chen, Xingxing Zhao, Qingang Hu, Yuxian Song, Yumei Pu, Zhiyong Wang, Wang Yujia, Liang Ding, Yue Jing, and Xiaoxin Zhang

Subjects
0301 basic medicine, Male, STAT3 Transcription Factor, Cancer Research, Stromal cell, Epithelial-Mesenchymal Transition, Mice, Nude, lcsh:RC254-282, Epiregulin, Metastasis, 03 medical and health sciences, Mice, 0302 clinical medicine, Downregulation and upregulation, Stroma, Invasion, Cancer-Associated Fibroblasts, Cell Line, Tumor, medicine, Animals, Humans, Neoplasm Invasiveness, STAT3, Mice, Inbred BALB C, biology, Chemistry, Research, Fibroblasts, Janus Kinase 2, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Xenograft Model Antitumor Assays, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Oncology, Oral squamous cell carcinoma, 030220 oncology & carcinogenesis, Transition, biology.protein, Cancer research, Carcinoma, Squamous Cell, Immunohistochemistry, Female, Mouth Neoplasms, Signal Transduction
Abstract

Background Local resident normal fibroblasts (NFs) are the major source of cancer-associated fibroblasts (CAFs), which are distinguishable from NFs by their tumor-supportive properties. However, the mechanism and the effects underlying the transition of NFs to CAFs in oral squamous cell carcinoma (OSCC) remain unclear. Methods Five pairs of matching primary NFs and CAFs derived from OSCC patients were sent for RNA sequencing. Epiregulin (EREG) expression was analyzed by IHC in fibroblasts from OSCC patients. The role of EREG in the NF-CAF transition and the consequential effects on OSCC progression were examined by upregulation/downregulation of EREG in NFs/CAFs both in vitro and in vivo. Results Here, we identified epiregulin (EREG) as the most remarkably upregulated gene in CAFs. High EREG expression in CAFs correlated with higher T stage, deeper invasion and inferior worst pattern of invasion (WPOI) in OSCC patients and predicted shorter overall survival. Overexpression of EREG in NFs activated the CAF phenotype. Mechanistically, the JAK2/STAT3 pathway was enhanced by EREG in parallel with increased IL-6 expression, which could be inhibited by the JAK2 inhibitor AG490. Recombinant IL-6 upregulated the JAK2/STAT3/EREG pathway in a feedback loop. Moreover, EREG-induced CAF activation promoted the epithelial-mesenchymal transition (EMT) necessary for migration and invasion, which was dependent on JAK2/STAT3 signaling and IL-6. In vivo, EREG expression in stroma fibroblasts promoted tumor growth with high stromal α-SMA, phospho-JAK2/STAT3, and IL-6 expression and upregulated EMT in HSC3 cells. Conclusions EREG is essential for the NF-CAF transformation needed to induce EMT of tumor cells in a JAK2-STAT3- and IL-6-dependent manner in OSCC. Electronic supplementary material The online version of this article (10.1186/s13046-019-1277-x) contains supplementary material, which is available to authorized users.

Published
2019

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