USP14/S100A11 axis promote colorectal cancer progression by inhibiting cell senescence.

The aberrant expression of S100A11 has been identified in various malignancies but its functional roles and underlying mechanisms in colorectal cancer (CRC) have not been fully elucidated. Therefore, this study was designed to investigate the expression of S100A11 and its functional significance in CRC, indicating that S100A11 is significantly upregulated and correlates with poor survival outcomes in CRC. Functionally, S100A11 knockdown in CRC cell lines inhibited cell proliferation, invasion, and migration, leading to decreased tumour growth and metastasis in vivo. Mechanistic investigations revealed that S100A11 promotes cell proliferation and invasion by suppressing cell senescence. In addition, USP14 interacts with and mediates S100A11 deubiquitination. More importantly, the overexpression of S100A11 was able to partially counteract the reduction in cell proliferation caused by the knockdown of USP14. In summary, the novel regulatory axis involving USP14 and S100A11 modulates the malignant biological behavior of CRC cells through inhibiting cell senescence, therefore the interaction between USP14 and S100A11 represents a promising therapeutic target in CRC.