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


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 ?-catenin or interacting with ?-catenin to compete with TCF for binding to ?-catenin. The carboxyl-terminus of SOX30 is required for attenuating ?-catenin transcriptional activity, whereas the amino-terminus of SOX30 is required for its interaction with ?-catenin protein. Enhance of ?-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.

SUBMITTER: Han F 

PROVIDER: S-EPMC6014586 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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

Han Fei F   Liu Wen-Bin WB   Shi Xiao-Yan XY   Yang Jun-Tang JT   Zhang Xi X   Li Zhi-Ming ZM   Jiang Xiao X   Yin Li L   Li Jian-Jun JJ   Huang Chuan-Shu CS   Cao Jia J   Liu Jin-Yi JY  

EBioMedicine 20180505


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<sup>-/-</sup> mice and this uncontrollable lung-metasta  ...[more]

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