SOX30 Inhibits Tumor Metastasis through Attenuating Wnt-Signaling via Transcriptional and Posttranslational Regulation of β-Catenin in Lung Cancer
Fei Han,
Wen-bin Liu,
Xiao-yan Shi,
Jun-tang Yang,
Xi Zhang,
Zhi-ming Li,
Xiao Jiang,
Li Yin,
Jian-jun Li,
Chuan-shu Huang,
Jia Cao,
Jin-yi Liu
Affiliations
Fei Han
Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China
Wen-bin Liu
Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China
Xiao-yan Shi
Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China
Jun-tang Yang
Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China
Xi Zhang
Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China
Zhi-ming Li
Translational Medicine Research Center, School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, PR China
Xiao Jiang
Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China
Li Yin
Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China
Jian-jun Li
Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing, PR China
Chuan-shu Huang
Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, New York, 10987, USA
Jia Cao
Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China; Corresponding authors at: Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, PR China.
Jin-yi Liu
Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China; Corresponding authors at: Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, PR China.
Although high mortality of lung cancer is greatly due to distant metastasis, the mechanism of this metastasis remains unclear. Here, we investigate in lung cancer that SOX30 is sharply under-expressed in metastatic tumors compared with non-metastatic tumors, and suppresses plenty of metastasis related processes or pathways. SOX30 strongly inhibits tumor cell metastasis in vitro and in vivo. Sox30 deficiency promotes lung metastasis in Sox30−/− mice and this uncontrollable lung-metastasis is re-inhibited upon Sox30 re-expression. Mechanistically, SOX30 diminishes Wnt-signaling via directly transcriptional repressing β-catenin or interacting with β-catenin to compete with TCF for binding to β-catenin. The carboxyl-terminus of SOX30 is required for attenuating β-catenin transcriptional activity, whereas the amino-terminus of SOX30 is required for its interaction with β-catenin protein. Enhance of β-catenin attenuates the anti-metastatic role of SOX30. Moreover, Sox30 deficiency promotes tumor metastasis and reduces survival of mice. In addition, nuclear SOX30 expression is closely associated with metastasis and represents a favorable independent prognostic biomarker of lung cancer patients. Altogether, these results highlight an important role and mechanism of SOX30 in lung cancer metastasis, providing a potential therapeutic target for anti-metastasis. Keywords: Lung cancer, Metastasis, SOX30, Wnt-signaling, Molecular mechanism
