The Activation of β₁-integrin by Type I Collagen Coupling with the Hedgehog Pathway Promotes the Epithelial-Mesenchymal Transition in Pancreatic Cancer

Title:The Activation of β₁-integrin by Type I Collagen Coupling with the Hedgehog Pathway Promotes the Epithelial-Mesenchymal Transition in Pancreatic Cancer

Volume: 14 Issue: 5

Author(s): Wanxing Duan, Jiguang Ma, Qingyong Ma, Qinhong Xu, Jianjun Lei, Liang Han, Xuqi Li, Zheng Wang, Zheng Wu, Shifang Lv, Zhenhua Ma, Mouzhu Liu, Fengfei Wang and Erxi Wu

Affiliation:

Keywords: Desmoplastic reaction, epithelial–mesenchymal transition, extracellular matrix, hedgehog pathway, β₁-integrin, pancreatic cancer.

Abstract: Pancreatic ductal adenocarcinoma (PDAC) is characterized by the excessive deposition of extracellular matrix (ECM), which is thought to contribute to this tumor’s malignant behavior. However, the detailed mechanism and the contribution of excessive deposition of ECM in PDAC progression remain unclear. A better understanding of the mechanism involved in this process is essential for the design of new effective therapies. In this study, we demonstrated that pancreatic cancer cells exhibited increased proliferation and decreased apoptosis in response to type I collagen. In addition, PDAC cells exposed to type I collagen lost the expression of E-cadherin and increased expression of mesenchymal markers, including N-cadherin and vimentin. This epithelial- mesenchymal transition (EMT) was correlated with enhanced cell migration and invasiveness. Knockdown of β₁-integrin abolished the effects induced by type I collagen, and further investigation revealed that type I collagen activates β₁-integrin (marked by phosphorylation of β₁ integrin downstream effectors, focal adhesion kinase [FAK], AKT, and ERK) accompanied by markedly up-regulation of Gli-1, a component of the Hedgehog (HH) pathway. Knockdown of Gli-1 reversed the effects of type I collagen on PDAC invasion and EMT. These results suggest that there is cross-talk between the β₁-integrin signaling pathway and the HH pathway in pancreatic cancer and that activation of the HH pathway plays a key role in the type I collagen-induced effects on pancreatic cancer.

Cite this article as:

Duan Wanxing, Ma Jiguang, Ma Qingyong, Xu Qinhong, Lei Jianjun, Han Liang, Li Xuqi, Wang Zheng, Wu Zheng, Lv Shifang, Ma Zhenhua, Liu Mouzhu, Wang Fengfei and Wu Erxi, The Activation of β₁-integrin by Type I Collagen Coupling with the Hedgehog Pathway Promotes the Epithelial-Mesenchymal Transition in Pancreatic Cancer, Current Cancer Drug Targets 2014; 14 (5) . https://dx.doi.org/10.2174/1568009614666140402105101