Tac2-N acts as a novel oncogene and promotes tumor metastasis via activation of NF-κB signaling in lung cancer

BACKGROUND: High rates of recurrence and metastasis are the major cause of the poor outcomes for patients with lung cancer. In previous research, we have demonstrated that Tac2-N promotes tumor growth by suppressing p53 signaling in lung cancer. Beyond that, other biological functions and clinical significance of Tac2-N in lung cancer progression are still unknown. METHODS: Tissue microarrays of 272 lung cancer patients were constructed to assess the association of Tac2-N expression and prognosis of lung cancer patients with different clinical stages. The protein expression of Tac2-N in metastatic and non-metastatic specimens were detected by IHC. In vitro migration and invasion and in vivo nude mice metastasis model were used to evaluate the effect of Tac2-N ectopic expression on metastasis capability of lung cancer cells. The downstream signaling pathway of Tac2-N was explored using luciferase reporter assays and WB. RESULTS: The expression of Tac2-N was associated with advanced stages, but not with early stages (P = 0.513). Tac2-N expression is sharply overexpressed in metastatic tumors compared with non-metastatic tumors. In vitro and in vivo assays suggested that Tac2-N facilitated migration and invasion of lung cancer cells in vitro and promoted tumor metastasis in vivo. Mechanistically, Tac2-N increased the degradation of IκB by promoting its phosphorylation, and subsequently activated NF-κB activity by facilitating the nuclear translocation of NF-κB and stimulating the transcription of targets, MMP7 and MMP9. Notably, the C2B domain of Tac2-N was crucial for Tac2-N to activate NF-κB signal. Blockage of NF-κB by shRNA or inhibitor attenuates the function of Tac2-N in the promotion of metastasis. CONCLUSIONS: Our study provided proof of principle to show that Tac2-N serves as a novel oncogene gene and plays an important role in the progression and metastasis of lung cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-019-1316-7) contains supplementary material, which is available to authorized users.