AI Article Synopsis
- Osteosarcoma is a highly aggressive cancer known for rapidly spreading to the lungs and currently lacks effective treatment targets.
- CBX4, which is found to be overexpressed in osteosarcoma cells, enhances metastasis by activating the Runx2 gene through GCN5 recruitment, while phosphorylation by CK1α leads to its degradation.
- The study suggests that CK1α can suppress metastasis, making it a potential prognostic marker and highlighting the CK1α/CBX4 pathway as a promising therapeutic target for osteosarcoma patients.
Article Abstract
Osteosarcoma, an aggressive malignant cancer, has a high lung metastasis rate and lacks therapeutic target. Here, we reported that chromobox homolog 4 (CBX4) was overexpressed in osteosarcoma cell lines and tissues. CBX4 promoted metastasis by transcriptionally up-regulating Runx2 via the recruitment of GCN5 to the Runx2 promoter. The phosphorylation of CBX4 at T437 by casein kinase 1α (CK1α) facilitated its ubiquitination at both K178 and K280 and subsequent degradation by CHIP, and this phosphorylation of CBX4 could be reduced by TNFα. Consistently, CK1α suppressed cell migration and invasion through inhibition of CBX4. There was a reverse correlation between CK1α and CBX4 in osteosarcoma tissues, and CK1α was a valuable marker to predict clinical outcomes in osteosarcoma patients with metastasis. Pyrvinium pamoate (PP) as a selective activator of CK1α could inhibit osteosarcoma metastasis via the CK1α/CBX4 axis. Our findings indicate that targeting the CK1α/CBX4 axis may benefit osteosarcoma patients with metastasis.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048933 | PMC |
| http://dx.doi.org/10.1038/s41467-020-14870-4 | DOI Listing |
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