Targeting the CK1α/CBX4 axis for metastasis in osteosarcoma

Xin Wang, Ge Qin, Xiaoting Liang, Wen Wang, Zhuo Wang, Dan Liao, Li Zhong, Ruhua Zhang, Yi-Xin Zeng, Yuanzhong Wu () and Tiebang Kang ()
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Xin Wang: Sun Yat-sen University Cancer Center
Ge Qin: Sun Yat-sen University
Xiaoting Liang: Sun Yat-sen University Cancer Center
Wen Wang: The Cancer Center of the Fifth Affiliated Hospital of Sun Yat-sen University
Zhuo Wang: Sun Yat-sen University
Dan Liao: Sun Yat-sen University Cancer Center
Li Zhong: Sun Yat-sen University Cancer Center
Ruhua Zhang: Sun Yat-sen University Cancer Center
Yi-Xin Zeng: Sun Yat-sen University Cancer Center
Yuanzhong Wu: Sun Yat-sen University Cancer Center
Tiebang Kang: Sun Yat-sen University Cancer Center

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-14870-4

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