TBX1 suppresses colorectal cancer cells via PPP2R2B-mediated inhibition of MAPK/ERK and PI3K/AKT pathways.

Background

Methods: To assess the impact of TBX1 on the proliferation and colony-forming capacity of colorectal cancer cells, in vitro functional investigations were carried out. Concurrently, a subcutaneous xenograft mouse model was established to determine the influence of TBX1 on tumor growth in vivo. Through a series of molecular and biochemical experiments, the underlying mechanism through which TBX1 exerts its effects in colorectal cancer cells was elucidated.

Results

Our findings revealed that TBX1 was significantly downregulated in colorectal cancers as compared to non-cancerous tissues. We showed that the ectopic expression of TBX1 potently inhibited cell proliferation, colony-forming ability, cell apoptosis, cell migration, cell invasion in colorectal cancer cells, and tumor growth in nude mice. This suppressive effect was achieved via the suppression of the MAPK/ERK and PI3K/AKT signaling pathways. Subsequent investigations indicated that TBX1 exerted its inhibitory influence on these two pathways by transcriptionally activating protein phosphatase 2 regulatory subunit B (PPP2R2B) directly, thereby fulfilling TBX1's tumor-suppressor functions. As anticipated, the knockdown of PPP2R2B remarkably alleviated the inhibitory impact of TBX1 on cell proliferation and colony formation. Moreover, it also significantly mitigated the inhibitory effects on the activities of the MAPK/ERK and PI3K/AKT pathways.

Conclusion

The current investigation demonstrates that TBX1 acts as a potential tumor suppressor in colorectal cancer cells by inhibiting the MAPK/ERK and PI3K/AKT signaling cascades depending on PPP2R2B.