Suppression of pancreatic adenocarcinoma upregulated factor (PAUF) increases the sensitivity of pancreatic cancer to gemcitabine and 5FU, and inhibits the formation of pancreatic cancer stem like cells

Jae Hee Cho; Sun A. Kim; Soo Been Park; Hee Man Kim; Si Young Song

doi:10.18632/oncotarget.19458

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Research Papers:

Suppression of pancreatic adenocarcinoma upregulated factor (PAUF) increases the sensitivity of pancreatic cancer to gemcitabine and 5FU, and inhibits the formation of pancreatic cancer stem like cells

Jae Hee Cho, Sun A. Kim, Soo Been Park, Hee Man Kim and Si Young Song _

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Oncotarget. 2017; 8:76398-76407. https://doi.org/10.18632/oncotarget.19458

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Abstract

Jae Hee Cho1,2,*, Sun A. Kim1,*, Soo Been Park1, Hee Man Kim3 and Si Young Song1,4

1Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea

2Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea

3Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea

4Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea

*These authors have contributed equally to this work

Correspondence to:

Si Young Song, email: [email protected]

Keywords: cancer stem cells, PAUF, pancreatic cancer, MRP5, RRM2

Received: March 03, 2017 Accepted: June 23, 2017 Published: July 22, 2017

ABSTRACT

Pancreatic cancer stem cells (CSCs) play a crucial role in tumorigenesis and chemoresistance of pancreatic ductal adenocarcinoma. Pancreatic adenocarcinoma up-regulated factor (PAUF), a novel secretory protein, has been shown to contribute to cancer progression and metastasis. Because the clinical relationship between PAUF and pancreatic CSCs is largely unknown, we investigated the associations between the functional role of PAUF and pancreatic CSCs. Pancreatic cancer sphere cultured from the CFPAC-1 cells showed elevated expression of PAUF and pluripotent stemness genes (Oct4, Nanog, Stat3, and Sox2), and the mRNA of PAUF were increased in CD44⁺CD24⁺ESA⁺ pancreatic CSCs. PAUF knockdown (shPAUF) CFPAC-1 diminished the number of spheres and decreased stemness genes and CSC surface markers (CD133, c-MET and ALDH1). In addition, siPAUF CFPAC-1 decreased the mRNA expression of multidrug resistant protein 5 (MRP5) and ribonucleotide reductase M2 (RRM2) and were more vulnerable to gemcitabine and 5-FU than negative control (p<0.05). In conclusion, PAUF was increased in pancreatic CSCs and the suppression of PAUF enhances chemotherapeutic response to gemcitabine and 5FU by decreasing MRP5 and RRM2 in pancreatic cancer cells.

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Research Papers:

Suppression of pancreatic adenocarcinoma upregulated factor (PAUF) increases the sensitivity of pancreatic cancer to gemcitabine and 5FU, and inhibits the formation of pancreatic cancer stem like cells

Abstract