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.