Thrombin-induced CCN2 expression in human lung fibroblasts requires the c-Src/JAK2/STAT3 pathway

Bai, Kua Jen; Chen, Bing Chang; Pai, Hui Chen; Weng, Chih Ming; Yu, Chung Chi; Hsu, Ming Jen; Yu, Ming Chih; Ma, Hon Ping; Wu, Chih Hsiung; Hong, Chien Tai; Kuo, Min-Liang; Lin, Chien Huang

doi:10.1189/jlb.0911449

Cited by 23 publications

(15 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tao et al have also demonstrated that there is an increase of JAK1 and STAT1 activity after CTGF stimulation of the human hypertrophic scar fibroblasts . In human lung fibroblasts, CCN2 expression is induced by JAK2's activation of STAT3 after JAK2 is activated by thrombin through its effect on c‐Src . The earlier studies all accord with what we have obtained in our study.…”

Section: Discussionsupporting

confidence: 92%

Upregulation of microRNA‐133a and downregulation of connective tissue growth factor suppress cell proliferation, migration, and invasion in human glioma through the JAK/STAT signaling pathway

et al. 2019

View full text Add to dashboard Cite

Recently, microRNA-133a (miR-133a) has been found to function in many diseases in previous studies, yet few studies have been focused on its role in glioma. This study aims to investigate the mechanism of miR-133a/CTGF on regulating the malignant phenotypes of glioma cells via the JAK/STAT signaling pathway. Sixty-five human glioma specimens were collected and 30 normal brain tissues were selected as controls. The expression of connective tissue growth factor (CTGF) and miR-133a in tissues was detected, and the relationship between their expression and the clinicopathological features as well as prognosis of glioma was analyzed. MiR-133a and CTGF expression in U87, A172, and HEB cell lines was determined. The expression of CTGF, signaling pathway-, proliferation-, migration-, invasion-, apoptosis-and epithelial-mesenchymal transition (EMT)-related factors was detected. A number of assays were used to detect cell proliferation, migration, invasion, cell cycle, apoptosis, glioma growth, and the targeting site between CTGF and miR-133a. MiR-133a was downregulated and CTGF was upregulated in human glioma tissues and cells. MiR-133a and CTGF expression was related to glioma's WHO staging and size. Downregulated miR-133a and upregulated CTGF caused unfavorable prognosis in glioma. Upregulated miR-133a suppressed CTGF expression and the activation of JAK/STAT signaling pathway, thereby constraining cell colony formation, proliferation, migration and invasion, and promoting apoptosis in glioma. Our study reveals that upregulated miR-133a and downregulated CTGF suppress cell proliferation, migration, and invasion in human glioma through the inhibition of the JAK/STAT signaling pathway.

show abstract

Section: Discussionsupporting

confidence: 92%

Upregulation of microRNA‐133a and downregulation of connective tissue growth factor suppress cell proliferation, migration, and invasion in human glioma through the JAK/STAT signaling pathway

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Growth factors, cytokines and hormones are classical regulators of CCN2, which include transforming growth factor (TGF)-β, bone morphogenetic protein (BMP)-2, angiotensin II, glucocorticoids, monocyte chemotactic protein (MCP)-1 and interferon (IFN)-γ [9][10][11]. Other extracellular signalling molecules, such as haemodynamic endothelin (ET)-1, secreted frizzled-like protein (sFRP)-2, anti-proliferative factor and thrombins are also reported to up-regulate CCN2 production [11,14,15]. In this point of view, one should note that induced CCN2 directly interacts with TGF-β molecules, which modulates its signalling [5].…”

Section: Gene Structure and Regulationmentioning

confidence: 99%

Cellular and molecular actions of CCN2/CTGF and its role under physiological and pathological conditions

2014

View full text Add to dashboard Cite

CCN family protein 2 (CCN2), also widely known as connective tissue growth factor (CTGF), is one of the founding members of the CCN family of matricellular proteins. Extensive investigation on CCN2 over decades has revealed the novel molecular action and functional properties of this unique signalling modulator. By its interaction with multiple molecular counterparts, CCN2 yields highly diverse and context-dependent biological outcomes in a variety of microenvironments. Nowadays, CCN2 is recognized to conduct the harmonized development of relevant tissues, such as cartilage and bone, in the skeletal system, by manipulating extracellular signalling molecules involved therein by acting as a hub through a web. However, on the other hand, CCN2 occasionally plays profound roles in major human biological disorders, including fibrosis and malignancies in major organs and tissues, by modulating the actions of key molecules involved in these clinical entities. In this review, the physiological and pathological roles of this unique protein are comprehensively summarized from a molecular network-based viewpoint of CCN2 functionalities.

show abstract

“…2D and E), indicating c-Src as the major downstream molecule of FAK. c-Src could activate STAT3 directly or indirectly through JAK2 (22,23). We demonstrated that CAFs had concomitantly elevated levels of p-c-Src, p-JAK2 and p-STAT3, which were markedly decreased in FAP À CAFs or FAK inhibitortreated CAFs (Fig.…”

Section: Fap Induces Inflammatory Fibroblasts By Activating Stat3 Thrmentioning

confidence: 77%

FAP Promotes Immunosuppression by Cancer-Associated Fibroblasts in the Tumor Microenvironment via STAT3–CCL2 Signaling

et al. 2016

View full text Add to dashboard Cite

Cancer-associated fibroblasts (CAF) are components of the tumor microenvironment whose contributions to malignant progression are not fully understood. Here, we show that the fibroblast activation protein (FAP) triggers induction of a CAF subset with an inflammatory phenotype directed by STAT3 activation and inflammation-associated expression signature marked by CCL2 upregulation. Enforcing FAP expression in normal fibroblasts was sufficient to endow them with an inflammatory phenotype similar to FAP þ CAFs. We identified FAP as a persistent activator of fibroblastic STAT3 through a uPAR-dependent FAK-Src-JAK2 signaling pathway. In a murine liver tumor model, we found that FAP þ CAFs were a major source of CCL2 and that fibroblastic STAT3-CCL2 signaling in this setting promoted tumor growth by enhancing recruitment of myeloid-derived suppressor cells (MDSC). The CCL2 receptor CCR2 was expressed on circulating MDSCs in tumor-bearing subjects and FAP þ CAF-mediated tumor promotion and MDSC recruitment was abrogated in Ccr2-deficient mice. Clinically, we observed a positive correlation between stromal expression of FAP, p-STAT3, and CCL2 in human intrahepatic cholangiocarcinoma, a highly aggressive liver cancer with dense desmoplastic stroma, where elevated levels of stromal FAP predicted a poor survival outcome. Taken together, our results showed how FAP-STAT3-CCL2 signaling in CAFs was sufficient to program an inflammatory component of the tumor microenvironment, which may have particular significance in desmoplasia-associated cancers. CancerRes; 76(14); 4124-35. Ó2016 AACR.

show abstract

Thrombin-induced CCN2 expression in human lung fibroblasts requires the c-Src/JAK2/STAT3 pathway

Cited by 23 publications

References 53 publications

Upregulation of microRNA‐133a and downregulation of connective tissue growth factor suppress cell proliferation, migration, and invasion in human glioma through the JAK/STAT signaling pathway

Upregulation of microRNA‐133a and downregulation of connective tissue growth factor suppress cell proliferation, migration, and invasion in human glioma through the JAK/STAT signaling pathway

Cellular and molecular actions of CCN2/CTGF and its role under physiological and pathological conditions

FAP Promotes Immunosuppression by Cancer-Associated Fibroblasts in the Tumor Microenvironment via STAT3–CCL2 Signaling

Contact Info

Product

Resources

About