14-3-3ζ/TGFβR1 promotes tumor metastasis in lung squamous cell carcinoma

14-3-3 zeta is involved in tumor cell growth and apoptosis. However, the mechanism of 14-3-3 zeta in lung squamous cell carcinoma (SCC) metastasis has not been illuminated. In our studies, we found that the expression of 14-3-3 zeta was highly expressed in lung SCC compared to normal lung tissues. High expression of 14-3-3 zeta was associated with pTNM stage (p< 0.05) and lymph node metastasis (p< 0.05). Furthermore, the expression of 14-3-3 zeta protein was associated with high levels of TGF beta R1 protein (p= 0.005), and pSMAD3 (p= 0.033). Lung SCC patients with high 14-3-3 zeta expression have significantly shorter OS and DFS compared to patients with low 14-3-3 zeta expression. Additionally, 14-3-3 zeta knockdown inhibited cell proliferation, migratory and invasive properties of human lung SCC cells. TGF beta R1 was involved in 14-3-3 zeta-mediated cell proliferation and metastasis of lung SCC cells. Additionally, sh-14-3-3 zeta can suppress tumor growth and metastasis in vivo. Thus, these data provide the evidence that 14-3-3 zeta promote tumor metastasis and might be a prognostic biomarker and target for therapeutic strategy in lung SCC.