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

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

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.

MeSH terms

  • Cell Line, Tumor
  • Humans
  • Keratin-13 / metabolism
  • Neoplastic Stem Cells / pathology
  • Pancreas
  • Pancreatic Neoplasms* / genetics
  • Pancreatic Neoplasms* / metabolism
  • Pancreatic Neoplasms* / radiotherapy
  • Radiation Tolerance* / genetics

Substances

  • KRT13 protein, human
  • Keratin-13