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Integrin β6 acts as an unfavorable prognostic indicator and promotes cellular malignant behaviors via ERK-ETS1 pathway in pancreatic ductal adenocarcinoma (PDAC)

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Tumor Biology

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most deadly cancers and is expected to become the second leading cause of cancer death by 2030. Despite extensive efforts to improve surgical treatment, limited progress has been made. Increasing evidence indicates that integrin β6 plays a crucial role in carcinoma invasion and metastasis. However, the expression and role of β6 in PDAC remain largely unknown. In the present study, we investigated the expression of β6 in PDAC and its potential value as a prognostic factor and therapeutic target. β6 upregulation was identified as an independent unfavorable prognostic indicator. Integrin β6 markedly promoted the proliferation and invasion of pancreatic carcinoma cells and induced ETS1 phosphorylation in an ERK-dependent manner, leading to the upregulation of matrix metalloprotease-9, which is essential for β6-mediated invasiveness of pancreatic carcinoma cells. Accordingly, small interfering RNA-mediated silencing of integrin β6 markedly suppressed xenograft tumor growth in vivo. Taken together, our results suggest that integrin β6 plays important roles in the progression of pancreatic carcinoma and contributes to reduced survival times, and may serve as a novel therapeutic target for the treatment of PDAC.

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Acknowledgments

This study is supported by National Natural Science Foundation of China (no. 81272653) and by Natural Science Foundation of Shandong Province (no. ZR2015HM071). The authors thank Biogen Idec for the special antibodies and Professor Hui Wang for the assistance in statistical analysis.

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    Authors and Affiliations

    1. Department of General Surgery, QiLu Hospital of Shandong University, Jinan, 250012, Shandong, China

      Zequn Li, Pengfei Lin, Chao Gao, Cheng Peng, Huijie Gao, Ben Wang, Jiayong Wang, Jun Niu & Weibo Niu

    2. Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Public Health, Jinan, 250012, Shandong, China

      Zequn Li & Pengfei Lin

    3. Department of Thyroid & Breast Surgery, Affiliated Hospital of Binzhou Medical College, Binzhou, 256603, Shandong, China

      Song Liu

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    1. Zequn Li
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    Zequn Li and Pengfei Lin contributed equally to this work.

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    Li, Z., Lin, P., Gao, C. et al. Integrin β6 acts as an unfavorable prognostic indicator and promotes cellular malignant behaviors via ERK-ETS1 pathway in pancreatic ductal adenocarcinoma (PDAC). Tumor Biol. 37, 5117–5131 (2016). https://doi.org/10.1007/s13277-015-4353-7

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