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Expression of concern
Open Access | 
10.1172/JCI213311
Expression of Concern for PIM3-mediated phosphorylation stabilizes myeloid leukemia factor 2 to promote metastasis in osteosarcoma
Cuiling Zeng, Xin Wang, Jinkun Zhong, Yu Zhang, Ju Deng, Wenqiang Liu, Weixuan Chen, Xinhao Yu, Dian Lin, Ruhua Zhang, Shang Wang, Jianpei Lao, Qi Zhao, Li Zhong, Tiebang Kang, and Dan Liao
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Published October 1, 2026 - More info
J Clin Invest. 2026;136(19):e213311. https://doi.org/10.1172/JCI213311.
© 2026 Zeng et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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Abstract
Osteosarcoma is the most common primary malignant bone cancer, characterized by a high incidence of lung metastasis and a lack of therapeutic targets. Here, by combining an in vivo CRISPR activation screen with the interactome of STUB1, a tumor suppressor in osteosarcoma, we identified that myeloid leukemia factor 2 (MLF2) promotes osteosarcoma metastasis. Mechanistically, MLF2 disrupted the interaction between BiP and IRE1α, thereby activating the IRE1α/XBP1-S-MMP9 axis. The E3 ligase STUB1 ubiquitinated MLF2 at Lys119 and targeted it for proteasomal degradation, whereas PIM3-mediated phosphorylation of MLF2 at Ser65 enhanced its stabilizing interaction with USP21. Our findings demonstrate that the PIM3/MLF2 axis is a critical regulator of osteosarcoma lung metastasis. We propose PIM3 as a potential therapeutic target for patients with osteosarcoma lung metastasis.
Authors
Cuiling Zeng, Xin Wang, Jinkun Zhong, Yu Zhang, Ju Deng, Wenqiang Liu, Weixuan Chen, Xinhao Yu, Dian Lin, Ruhua Zhang, Shang Wang, Jianpei Lao, Qi Zhao, Li Zhong, Tiebang Kang, Dan Liao
Original citation: J Clin Invest. 2025;135(20):e191040. https://doi.org/10.1172/JCI191040
Citation for this expression of concern: J Clin Invest. 2026;136(19):e213311. https://doi.org/10.1172/JCI213311
The authors recently alerted the Editors to errors in the source data for Figure 1G and Supplemental Figure 10K as well as errors in the statistical analysis of Figure 2, Q–T and Figure 5R that were identified in response to an institutional mandate for a post-publication audit of the data. Although the authors have indicated that the errors were due to inadvertent mistakes, the Editors are issuing this Expression of Concern to alert readers to the issues. We have requested institutional oversight into this matter and will alert readers to the outcome when the institutional evaluation is complete.
Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)