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. 2023 Mar 23;64(2):284-293.
doi: 10.1093/jrr/rrac091.

KRT13 is upregulated in pancreatic cancer stem-like cells and associated with radioresistance

Wataru Takenaka  1 , Yuhki Yokoyama  2 , Katsuya Ikehata  1 , Shihori Kouda  2 , Haruka Hirose  3 , Kazumasa Minami  1 , Yoshinosuke Hamada  4   5 , Seiji Mori  6 , Masahiko Koizumi  1 , Hirofumi Yamamoto  2   7
Affiliations

KRT13 is upregulated in pancreatic cancer stem-like cells and associated with radioresistance

Wataru Takenaka et al. J Radiat Res. .

Abstract

Pancreatic 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.

Keywords: KRT13; cancer stem-like cell (CSC); pancreatic cancer; radioresistance.

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Conflict of interest statement

The authors declare no potential conflicts of interest.

Figures

Fig. 1
Fig. 1
Generation of a pancreatic CSC model by use of the ODC-degron system. A. Photomicrograph of degron (−) cells. The percentage of ZsGreen-positive cells was less than 1%. B. Photomicrograph of degron (+) cells. The percentage of ZsGreen-positive cells was more than 40%. C. The expression levels of ZsGreen in the degron (−) and degron (+) cell populations. The 50% of cells with the highest ZsGreen expression (blue color) were defined as degron (++) cells and used for the subsequent experiments. D. The number of CD44v9 and CD133 double positive population in degron (−) and degron (++) cells. The number relative to the control cells (degron (−)) are shown. Each bar represents the mean ± standard deviation (*  P < 0.05). E. The number of spheroids in degron (−) and degron (++). Spheroids (>100 um) were counted on day 5 after seeding. Each bar represents the mean ± standard deviation (*  P < 0.05).
Fig. 2
Fig. 2
Radioresistance was higher in degron (++) cells than in degron (−) cells. A. Flow cytometry analysis of annexin V–positive (X axis) and 7-AAD–positive (Y axis) cells 72 hours after irradiation of degron (−) and degron (++) cells. B. Bar chart of the apoptotic cells (annexin V–positive cells) shown in Fig. 2A. Each bar represents the mean ± standard deviation (**  P < 0.01). C. Cell viability of degron (−) and degron (++) cells fourteen days after irradiation. The values relative to the control cells (no irradiation) is shown. Each bar represents the mean ± standard deviation (**  P < 0.01).
Fig. 3
Fig. 3
KRT13 knockdown decreased radioresistance and stem-like cell property in degron (++) cells. A. Flow cytometry analysis of annexin V–positive (X axis) and 7-AAD–positive (Y axis) cells 72 hours after the irradiation of siNC- and siKRT13-treated degron (++) cells. B. Bar chart of the apoptotic cells (annexin V–positive cells) shown in Fig 3A. Each bar represents the mean ± standard deviation (*  P < 0.05). C. Viability of siNC- and siKRT13-treated degron (++) cells fourteen days after irradiation. Values relative to the control cells (no radiation) are shown. Each bar represents the mean ± standard deviation (**  P < 0.01). D. The number of CD44v9 and CD133 double positive population in siNC- and siKRT13-treated degron (++) cells. The number relative to the control cells (siNC-treated) are shown. Each bar represents the mean ± standard deviation (**  P < 0.01). E. The number of spheroids in siNC- and siKRT13-treated degron (++) cells. Spheroids (>100 um) were counted on day 5 after seeding. Each bar represents the mean ± standard deviation (**  P < 0.01).
Fig. 4
Fig. 4
KRT13 is upregulated in pancreatic cancer cell lines, and high KRT13 expression is associated with poorer prognosis in pancreatic cancer. A. KRT13 expression levels in multiple cancer cell lines registered in the CCLE database. B. Patient survival in KRT13low and KRT13high expression groups in pancreatic cancer. The analysis was performed by using the OncoLnc web tool. P < 0.0001.
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References

    1. Sung H, Ferlay J, Siegel RL et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209–49. - PubMed
    1. Hall WA, Goodman KA. Radiation therapy for pancreatic adenocarcinoma, a treatment option that must be considered in the management of a devastating malignancy. Radiat Oncol 2019;14:19–23. - PMC - PubMed
    1. Boyle J, Czito B, Willett C, Palta M. Adjuvant radiation therapy for pancreatic cancer: a review of the old and the new. J Gastrointest Oncol 2015;6:436–44. - PMC - PubMed
    1. Khan AQ, Rashid K, AlAmodi AA et al. Recent developments in unraveling signaling mechanisms underlying drug resistance due to cancer stem-like cells. Curr Opin Pharmacol 2020;54:130–41. - PubMed
    1. Baek SJ, Ishii H, Tamari K et al. Cancer stem cells: the potential of carbon ion beam radiation and new radiosensitizers (review). Oncol Rep 2015;34:2233–7. - PubMed