KRT13is upregulated in pancreatic cancer stem-like cells and associated with radioresistance

Author:

Takenaka Wataru1,Yokoyama Yuhki2,Ikehata Katsuya1,Kouda Shihori2,Hirose Haruka3,Minami Kazumasa1,Hamada Yoshinosuke45,Mori Seiji6,Koizumi Masahiko1,Yamamoto Hirofumi27

Affiliation:

1. Department of Medical Physics and Engineering, Division of Health Sciences, Graduate School of Medicine, Osaka University , 1-7 Yamadaoka, Suita city, Osaka, 565-0871 , Japan

2. Department of Molecular Pathology, Division of Health Sciences, Graduate School of Medicine, Osaka University , 1-7 Yamadaoka, Suita city, Osaka, 565-0871 , Japan

3. Department of Systems Biology, Graduate School of Medicine, Nagoya University , 65 Tsurumai-cho, Showa-ku, Nagoya city, Nagoya, 466-8550 , Japan

4. Department of Health Economics and Management, Graduate School of Medicine, Osaka University , 1-7 Yamadaoka, Suita city, Osaka, 565-0871 , Japan

5. Department of Pediatric Dentistry, School of Dentistry, Osaka Dental University , 8-1  Kuzuhahanazono-cho, Hirakata city, Osaka, 573-1121 , Japan

6. Department of Medical Technology, Faculty of Health Sciences, Morinomiya University of Medical Sciences , 1-26-16 Nankokita, Suminoe-ku, Osaka city, Osaka, 559-8611 , Japan

7. Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University , 2-2 Yamadaoka, Suita city, Osaka, 565-0871 , Japan

Abstract

AbstractPancreatic cancer is one of the most aggressive cancers and the seventh leading cause of cancer-associated death in the world. Radiation is performed as an adjuvant therapy as well as anti-cancer drugs. Because cancer stem-like cells (CSCs) are considered to be radioresistant and cause recurrence and metastasis, understanding their properties is required for the development of novel therapeutic strategies. To investigate the CSC properties of pancreatic cancer cells, we used a pancreatic CSC model, degron (++) cells, which have low proteasome activity. Degron (++) cells displayed radioresistance in comparison with control cells. Using Ribonucleic acid (RNA) sequencing, we successfully identified KRT13 as a candidate gene responsible for radioresistance. Knockdown of KRT13 sensitized the degron (++) cells to radiation. Furthermore, a database search revealed that KRT13 is upregulated in pancreatic cancer cell lines and that high expression of KRT13 is associated with poorer prognosis. These results indicate that a combination therapy of KRT13 knockdown and radiation could hold therapeutic promise in pancreatic cancer.

Funder

Kagoshima Shinsangyo Sousei Investment Limited Partnership

Publisher

Oxford University Press (OUP)

Subject

Health, Toxicology and Mutagenesis,Radiology, Nuclear Medicine and imaging,Radiation

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