2. Academic Validation
  3. CCT5 maintains mitotic fidelity and promotes early colorectal tumorigenesis

CCT5 maintains mitotic fidelity and promotes early colorectal tumorigenesis

  • iScience. 2026 Mar 4;29(4):115223. doi: 10.1016/j.isci.2026.115223.
Meijun Ji 1,  Wenhan Zhuang 2,  Yumin Guo 1,  Pengfei Xu 2,  Xiaolu Zhou 1,  Yan Long 3,  Xiaoge Geng 1,  Jiyong Jing 4,  Xuelong Zhou 5,  Wensheng Pan 1,  Chenjing Zhang 1
Affiliations

Affiliations

  • 1 Cancer Center, Department of Gastroenterology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, No.158 Shangtang Road, Hangzhou, Zhejiang, China.
  • 2 The Second School of Clinical Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China.
  • 3 Obsterics & Gynecology Hospital of Fudan University, Yangtze River Delta Integration Demonstration Zone (QingPu), Shanghai, China.
  • 4 Department of Medical Education and Simulation Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, Zhejiang, China.
  • 5 Department of Anesthesiology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
PMID: 41890968 DOI: 10.1016/j.isci.2026.115223
Abstract

Colorectal Cancer (CRC) is a leading cause of cancer-related mortality, and early tumorigenesis is closely associated with mitotic dysregulation and chromosomal instability. To define molecular mechanisms supporting mitotic fidelity during CRC initiation, we combined multi-omics profiling, genetically engineered mouse models, and functional assays to examine the role of the chaperonin subunit CCT5. Transcriptomic and proteomic analyses revealed elevated CCT5 expression in stage I CRC and precancerous lesions, indicating diagnostic relevance. The genetic depletion of CCT5 suppressed epithelial proliferation, reduced dysplastic transformation, and limited tumor initiation in vivo. In CRC cells, CCT5 silencing impaired proliferation and induced G2/M arrest. Mechanistically, CCT5 interacts with CDC20 and facilitates turnover of the MCC-CDC20-APC/C complex, enabling metaphase-to-anaphase progression. These findings position CCT5 as a regulator of early CRC development with implications for early detection and therapeutic intervention.

Keywords

Cancer; Molecular interaction; Molecular network.

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