Research Papers:

Tenascin-C induces migration and invasion through JNK/c-Jun signalling in pancreatic cancer

Jun Cai, Shaoxia Du, Hui Wang, Beibei Xin, Juan Wang, Wenyuan Shen, Wei Wei, Zhongkui Guo and Xiaohong Shen _

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Oncotarget. 2017; 8:74406-74422. https://doi.org/10.18632/oncotarget.20160

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Jun Cai1, Shaoxia Du1, Hui Wang1, Beibei Xin1, Juan Wang1, Wenyuan Shen1, Wei Wei2, Zhongkui Guo1 and Xiaohong Shen1

1School of Medicine, Nankai University, Tianjin 300071, China

2Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China

Correspondence to:

Xiaohong Shen, email: [email protected]

Keywords: TNC, JNK/c-Jun, EMT, pancreatic cancer

Received: December 28, 2016    Accepted: June 20, 2017    Published: August 10, 2017


Tenascin-C (TNC), a large extracellular matrix glycoprotein, has been reported to be associated with metastasis and poor prognosis in pancreatic cancer. However, the effects and mechanisms of TNC in pancreatic cancer metastasis largely remain unclear. We performed Transwell assays to investigate the effects of TNC on Capan-2, AsPC-1 and PANC-1 cells. In addition, western blot and RT-qPCR assays were used to examine potential TNC metastasis-associated targets, such as JNK/c-Jun, Paxillin/FAK, E-cadherin, N-cadherin, Vimentin, and MMP9/2. Lastly, we utilized a variety of methods, such as immunofluorescence, gelatin zymography and immunoprecipitation, to determine the molecular mechanisms of TNC in pancreatic cancer cell motility. The present study showed that TNC induced migration and invasion in pancreatic cancer cells and regulated a number of metastasis-associated proteins, including the EMT markers, MMP9 and Paxillin. Moreover, our data showed that TNC induced pancreatic cancer cells to generate an EMT phenotype and acquire motility potential through the activation of JNK/c-Jun signalling. In addition, TNC increased the DNA binding activity of c-Jun to the MMP9 promoter, an action likely resulting in increased MMP9 expression and activity. TNC/JNK also markedly induced the phosphorylation of Paxillin on serine 178, which is critical for the association between FAK and Paxillin and promoted the formation of focal adhesions. TNC/JNK initiates cell migration and invasion of pancreatic cancer cells through the promotion of EMT, the transactivation of MMP9 and the phosphorylation of Paxillin on serine 178. TNC may be a potential therapeutic target for treating pancreatic cancer metastasis.

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