Therefore, we hypothesized that exogenous fibronectin binds to integrin on the cell surface to activated downstream signaling pathways such as FAK and MAPK/ERK, which mediated the accumulation of HIF-1α, then, activated HIF-1α and elevated the transcription of WISP3, thus the up-regulation of WISP3 promoted the activation of Wnt signaling pathway, and finally enhanced the tumor growth, metastasis, and angiogenesis in NSCLC (Fig. 9). This evidence concerns the gene FN1 and non-small cell lung carcinoma.