Salinomycin effectively eliminates cancer stem-like cells and obviates hepatic metastasis in uveal melanoma
Authors: Jingxuan Pan
Wei Dai
Jingfeng Zhou
Shubo Wang
Yun Wang
Hailin Zou
Jing Zhang
Shenglan Liu
Journal: Molecular cancer (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Cancer stem-like cells; Metastasis; Salinomycin; Twist1; Uveal melanoma.
Affiliations: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 South Xianlie Road, Guangzhou, 510060, People's Republic of China., State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 South Xianlie Road, Guangzhou, 510060, People's Republic of China. .

Abstract:  Background: Uveal melanoma (UM) is the most common primary intraocular tumor. Hepatic metastasis is the major and direct death-related reason in UM patients. Given that cancer stem-like cells (CSCs) are roots of metastasis, targeting CSCs may be a promising strategy to overcome hepatic metastasis in UM. Salinomycin, which has been identified as a selective inhibitor of CSCs in multiple types of cancer, may be an attractive agent against CSCs thereby restrain hepatic metastasis in UM. The objective of the study is to explore the antitumor activity of salinomycin against UM and clarify its underlying mechanism. Methods: UM cells were treated with salinomycin, and its effects on cell proliferation, apoptosis, migration, invasion, CSCs population, and the related signal transduction pathways were determined. The in vivo antitumor activity of salinomycin was evaluated in the NOD/SCID UM xenograft model and intrasplenic transplantation liver metastasis mouse model. Results: We found that salinomycin remarkably obviated growth and survival in UM cell lines and in a UM xenograft mouse model. Meanwhile, salinomycin significantly eliminated CSCs and efficiently hampered hepatic metastasis in UM liver metastasis mouse model. Mechanistically, Twist1 was fundamental for the salinomycin-enabled CSCs elimination and migration/invasion blockage in UM cells. Conclusions: Our findings suggest that targeting UM CSCs by salinomycin is a promising therapeutic strategy to hamper hepatic metastasis in UM. These results provide the first pre-clinical evidence for further testing of salinomycin for its antitumor efficacy in UM patients with hepatic metastasis. 

Retracted: No

PubPeer comments:
 The two flow cytometry images in Fig. 2A look identical with different gating ratios. Could the authors please check? ![file] The two images in Fig. 2D look also identical with different gating ratios. ![file] , 
 #1 Dear Dr. Platycheirus Stegnus, I am the first author Jingfeng Zhou. Thank you very much for pointing out the two errors in Fig. 2A and Fig.2D. I have carefully checked our original data, and found that they were indeed errors which inadvertently took place during the stage of figure preparation with photoshop microsoftware. 1. In Fig. 2A, the diagram of flow cytometry in 2.5 uM Salinomycin-treated 92.1 cells group was wrongly duplicated with that of control. The corrected diagram and its source are shown below. ![file] 2. In Fig. 2D, the diagram of flow cytometry in Omm2.3 cells treated for 24 h was wrongly duplicated with that in Omm2.3 cells treated for 18 h. The corrected one and its source are shown below. ![file] These two errors did not affect the conclusions of the study. We deeply apologize for these unconscious mistakes during figure assembly. The authors will write to the Journal to request an erratum. Thanks. Jingfeng Zhou. ,