Oncotarget

Research Papers:

Role of transgelin-2 in diabetes-associated pancreatic ductal adenocarcinoma

Yan Sun, Weiwei He, Man Luo, Yuhong Zhou, Guilin Chang, Weiying Ren, Kefen Wu, Xi Li, Jiping Shen, Xiaoping Zhao _ and Yu Hu

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Oncotarget. 2017; 8:49592-49604. https://doi.org/10.18632/oncotarget.17519

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Abstract

Yan Sun1,*, Weiwei He2,*, Man Luo1, Yuhong Zhou3, Guilin Chang1, Weiying Ren1, Kefen Wu1, Xi Li1, Jiping Shen1, Xiaoping Zhao4 and Yu Hu1

1Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai 200032, China

2Department of Thoracic Surgery, Sixth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China

3Department of Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China

4Department of Nuclear Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China

*These authors have contributed equally to this work

Correspondence to:

Xiaoping Zhao, email: [email protected]

Yu Hu, email: [email protected]

Keywords: transgelin-2, SREBP, PDAC, diabetes, insulin

Received: June 29, 2016    Accepted: March 29, 2017    Published: April 29, 2017

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis. Diabetes is a significant risk factor for PDAC and >50% of PDAC patients have concomitant diabetes. How diabetes influences the initiation and progression of PDAC remains elusive. Here, we show that transgelin-2 is dominantly expressed in PDAC tissues compared with adjacent normal tissues. The high level of transgelin-2 indicates poor survival of patients with PDAC. Remarkably, transgelin-2 expression is correlated with diabetic status. Hyperinsulinemia is frequently observed in type 2 diabetes. Our results indicate that upregulation of transgelin-2 is induced by insulin via sterol regulatory element-binding protein (SREBP)-1-mediated transcription in PDAC cells. Transgelin-2 is a novel target of SREBP-1. Our data support a novel mechanism in diabetes-associated PDAC by which transgelin-2 mediates proliferation of PDAC cells upon insulin stimulation. The insulin/SREBP-1/transgelin-2 network should be further explored as a diagnostic marker or a novel therapeutic target for diabetes-associated PDAC.


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