CCN6 and neoplasm: 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).