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

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)76398-76407
Number of pages10
JournalOncotarget
Volume8
Issue number44
DOIs
Publication statusPublished - 2017

Bibliographical note

Funding Information:
This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education (Jae Hee Cho, No. NRF-2017R1D1A1B04034547). In addition, this research was supported by a grant (Si Young Song) of the Korean Heath Technology R&D Project (A111075), Ministry of Health & Welfare and by a grant of Korean Heath Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI14C1324).

Publisher Copyright:
© Cho et al.

All Science Journal Classification (ASJC) codes

  • Oncology

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