# CCT5 maintains mitotic fidelity and promotes early colorectal tumorigenesis

## TL;DR

CCT5 helps cells divide properly and is linked to early colorectal cancer, suggesting it could be a target for early detection and treatment.

## Contribution

This study identifies CCT5 as a novel regulator of mitotic fidelity and early colorectal tumorigenesis.

## Key findings

- CCT5 is upregulated in early-stage CRC and precancerous lesions.
- CCT5 loss suppresses epithelial proliferation and tumor initiation in vivo.
- CCT5 regulates the MCC-CDC20–APC/C complex to ensure metaphase-to-anaphase progression.

## 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.

•CCT5 is upregulated in early-stage CRC and precancerous lesions•CCT5 loss suppresses epithelial proliferation and tumor initiation in vivo•CCT5 ensures metaphase-anaphase transition by regulating MCC-CDC20-APC/C•CCT5 supports mitotic fidelity and represents a target for early CRC detection

CCT5 is upregulated in early-stage CRC and precancerous lesions

CCT5 loss suppresses epithelial proliferation and tumor initiation in vivo

CCT5 ensures metaphase-anaphase transition by regulating MCC-CDC20-APC/C

CCT5 supports mitotic fidelity and represents a target for early CRC detection

Molecular interaction; Molecular network; Cancer