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

Abstract

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.

Tenascin-C predicts poor outcomes for patients with colorectal cancer and drives cancer stemness via Hedgehog signaling pathway

“…Cai et al demonstrated that TNC was essential to trigger migration and invasion in pancreatic cancer both in vitro and in vivo [17]. Similarly, the CDK4 and Fig.…”

Differential impact of CX3CL1 on lung cancer prognosis in smokers and non‐smokers

“…MMPs have been shown to be regulated by MAPK pathways in various systems . We investigated the phosphorylation of Extracellular signal‐regulated kinase (ERK), p38 mitogen‐activated protein kinases (p38 MAPK), and Jun N‐terminal kinase (JNK) following CX3CL1 knockdown, and observed that phospho‐JNK, total JNK, and phosphor‐ERK expression levels all decrease (Figure A).…”

“…MMPs have been shown to be regulated by MAPK pathways in various systems. [15][16][17][18][19][20] We investigated the phosphorylation of Extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinases…”

c-Jun Overexpression Accelerates Wound Healing in Diabetic Rats by Human Umbilical Cord-Derived Mesenchymal Stem Cells

“…In addition, c-Jun drives cell proliferation by downregulating p53 [32,33]. c-Jun also regulates the migration of various cell types such as cancer cells during metastasis [34,35] and epithelial cells during embryogenesis [36]. The wound healing process mainly involves the proliferation and migration of cells, primarily keratinocytes and fibroblasts, and the formation of new blood vessels (angiogenesis); therefore, it is not surprising that c-Jun plays a fundamental role in wound healing [21,37].…”