SOX30 Inhibits Tumor Metastasis through Attenuating Wnt-Signaling via Transcriptional and Posttranslational Regulation of β-Catenin in Lung Cancer

  • EBioMedicine. 2018 May;31:253-266. doi: 10.1016/j.ebiom.2018.04.026.
Fei Han  1 ,  Wen-Bin Liu  1 ,  Xiao-Yan Shi  1 ,  Jun-Tang Yang  1 ,  Xi Zhang  1 ,  Zhi-Ming Li  2 ,  Xiao Jiang  1 ,  Li Yin  1 ,  Jian-Jun Li  3 ,  Chuan-Shu Huang  4 ,  Jia Cao  5 ,  Jin-Yi Liu  6
Affiliations
  • 1. Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China.
  • 2. Translational Medicine Research Center, School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, PR China.
  • 3. Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing, PR China.
  • 4. Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, New York, 10987, USA.
  • 5. Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China. Electronic address: [email protected].
  • 6. Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China. Electronic address: [email protected].
PMID: 29739711 DOI: 10.1016/j.ebiom.2018.04.026
Abstract

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; Molecular mechanism; SOX30; Wnt-signaling.