期刊
EBIOMEDICINE
卷 31, 期 -, 页码 253-266出版社
ELSEVIER
DOI: 10.1016/j.ebiom.2018.04.026
关键词
Lung cancer; Metastasis; SOX30; Wnt-signaling; Molecular mechanism
资金
- National Natural Science Foundation of China [81502551, 81172714]
- Postdoctoral Science Foundation special funded project of Chongqing [Xm2014122]
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 beta-catenin or interacting with beta-catenin to compete with TCF for binding to beta-catenin. The carboxyl-terminus of SOX30 is required for attenuating beta-catenin transcriptional activity, whereas the amino-terminus of SOX30 is required for its interaction with beta-catenin protein. Enhance of beta-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. (C) 2018 The Authors. Published by Elsevier B.V.
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