Kinesin Family Member 26A Disrupts DNA-Dependent Protein Kinase Complex Formation to Enhance Chemoradiotherapy Sensitivity in Colorectal Cancer

Sep 22, 2026

Upload by Maeve

Chemoradiotherapy is the principal approach for treating a wide range of human cancers, yet clinical benefit is often limited by tumor chemoradiotherapy resistance. Kinesin family member 26A (KIF26A) is downregulated in chemoradioresistant colorectal cancers, and reduced KIF26A predicts poorer chemoradiotherapy responsiveness and worse patient outcomes. Mechanistically, KIF26A suppresses DNA-dependent protein kinase (DNA-PK) complex formation via Ku70 interaction, blocking NHEJ activation and impairing DNA damage repair. Histone deacetylase inhibitors (HDACi) restore KIF26A expression and enhance sensitivity in KIF26A-low cells.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages21

Reading Time53 min

AccessFree to download

Abstract

Introduction

Ivyspring International Publisher InternationalJournal of Biological Sciences 2026; 22(7): 3411-3431. doi: 10.7150/ijbs.127218 Research Paper Kinesin Family Member 26A Disrupts DNA-Dependent Protein Kinase Complex Formation to Enhance Chemoradiotherapy Sensitivity in Colorectal Cancer Mengjie Li1, Ningxin Ren1, Shaosen Zhang1, Hongxia Chen1, Ruoqing Yan1, Ying Huang1,2, Jing Jin3,4, Linlin Zheng1, Shuangmei Zou5, Yexiong Li3, Wen Tan1􀀍, Dongxin Lin1,6􀀍 1. State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. 2. Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China. 3. Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. 4. Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518100, China. 5. Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. 6. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, China. 􀀍 Corresponding authors: Wen Tan, State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. E-mail: [tanwen@cicams.ac.cn. Phone:](tanwen@cicams.ac.cn. Phone:) +86-010-8778-8349. Dongxin Lin, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. E-mail: [lindx@cicams.ac.cn. Phone:](lindx@cicams.ac.cn. Phone:) +86-010-8778-8491. © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)). See [https://ivyspring.com/terms](https://ivyspring.com/terms) for full terms and conditions. Received: 2025.10.23; Accepted: 2026.03.07; Published: 2026.03.17 Abstract Chemoradiotherapy is the principal approach for treating a wide range of human cancers. However, its therapeutic outcomes in clinical settings are frequently impaired by resistance to tumor chemoradiotherapy. In this study, we demonstrated that kinesin family member 26A (KIF26A) is downregulated in chemoradioresistant colorectal cancers, as revealed by transcriptomic analyses of colorectal cancer tissues and cell lines. Reduced KIF26A levels predicted diminished responsiveness to chemoradiotherapy and unfavorable outcomes in patients with colorectal cancer. Furthermore, lower KIF26A expression was associated with colorectal cancer (CRC) progression, migration, and invasion. This is the first demonstration that KIF26A interacts with Ku70 to suppress the formation of the DNA-dependent protein kinase (DNA-PK) complex, thereby preventing activation of non-homologous end joining (NHEJ) for repairing DNA damage. This makes cancer cells more vulnerable to DNA damage from chemoradiotherapy, thereby enhancing their sensitivity. To address chemoradio-resistance in KIF26A-low-expressing cells, we ascertained that histone deacetylase

FAQs

What role does KIF26A play in chemoradiotherapy resistance in colorectal cancer?

KIF26A is downregulated in chemoradioresistant colorectal cancers. Lower KIF26A predicts reduced responsiveness to chemoradiotherapy and unfavorable patient outcomes.

How does KIF26A affect DNA repair during chemoradiotherapy?

KIF26A interacts with Ku70 to suppress formation of the DNA-dependent protein kinase (DNA-PK) complex, preventing activation of non-homologous end joining (NHEJ) for repairing DNA damage.

Why are histone deacetylase inhibitors (HDACi) relevant to overcoming resistance?

In KIF26A-low-expressing cells, HDACi increase acetylation of the KIF26A promoter, upregulate KIF26A, and boost sensitivity to chemoradiotherapy-resistant cells.

Sep 22, 2026

Upload by Maeve