CCT5 maintains mitotic fidelity and promotes early colorectal tumorigenesis
Meijun Ji, Wenhan Zhuang, Yumin Guo, Pengfei Xu, Xiaolu Zhou, Yan Long, Xiaoge Geng, Jiyong Jing, Xuelong Zhou, Wensheng Pan, Chenjing Zhang
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.
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…
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Taxonomy
TopicsHippo pathway signaling and YAP/TAZ · Cancer Cells and Metastasis · FOXO transcription factor regulation