Research Papers:

IL-6 secreted by cancer-associated fibroblasts promotes epithelial-mesenchymal transition and metastasis of gastric cancer via JAK2/STAT3 signaling pathway

Xiongyan Wu, Pan Tao, Quan Zhou, Jie Li, Zhenjia Yu, Xiaofeng Wang, Jiaanfang Li, Chen Li, Min Yan, Zhenggang Zhu, Bingya Liu and Liping Su _

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Oncotarget. 2017; 8:20741-20750. https://doi.org/10.18632/oncotarget.15119

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Xiongyan Wu1,*, Pan Tao1,*, Quan Zhou1,*, Jie Li1, Zhenjia Yu1, Xiaofeng Wang1, Jiaanfang Li1, Chen Li1, Min Yan1, Zhenggang Zhu1, Bingya Liu1, Liping Su1

1Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, People’s Republic of China

*These authors contributed equally to this work

Correspondence to:

Liping Su, email: [email protected]

Keywords: cancer-associated fibroblasts, interleukin-6, JAK/STAT3, gastric cancer

Received: July 22, 2016     Accepted: January 23, 2017     Published: February 06, 2017


Cancer-associated fibroblasts (CAFs), as the activated fibroblasts in tumor stroma, are important modifiers of tumor progression. However, the molecular mechanisms underlying the tumor-promoting properties of CAFs in gastric cancer remain unclear. Here, we show that CAFs isolated from gastric cancer produce significant amounts of interleukin-6 (IL-6). CAFs enhances the migration and EMT of gastric cancer cells through the secretion of IL-6 that activates Janus kinase 2/signal transducers and activators of transcription (JAK2/STAT3) pathway in gastric cancer cells, while deprivation of IL-6 using a neutralizing antibody or inhibition of JAK/STAT3 pathway with specific inhibitor AG490 markedly attenuates these phenotypes in gastric cancer cells induced by CAFs. Moreover, silencing IL-6 expression in CAFs or inhibiting JAK2/STAT3 pathway in gastric cancer cells impairs tumor peritoneal metastasis induced by CAFs in vivo. Taken together, these results suggest that CAFs in the tumor microenvironment promote the progression of gastric cancer through IL-6/JAK2/STAT3 signaling, and IL-6 targeted therapy could be a complementary approach against gastric cancer by exerting their action on stromal fibroblasts.

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