WISP3 upregulates SDCBP expression to promote the progression of non-small cell lung cancer via the TGF-β signaling pathway.

Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases, posing a major health burden. Our prior work indicated fibronectin promotes NSCLC angiogenesis and progression by upregulating Wnt-inducible signaling pathway protein 3 (WISP3) and activating Wnt signaling. This study aims to explore WISP3's role and mechanisms in NSCLC progression. Cells were transfected with a reconstructed plasmid to study gene overexpression/silencing effects. Functional assays were conducted, including tube formation, sphere formation, immunohistochemistry, western blotting, Transwell, and MTT. Mass spectrometry and bioinformatics analysis were used to identify differentially expressed proteins and their associated signaling pathways in NSCLC cells. Additionally, the xenograft tumor model of NSCLC was constructed. High expression of WISP3 in NSCLC is associated with poor prognosis, as it enhances angiogenic and tumorigenic potential in NSCLC cells, further verified in our constructed xenograft tumor experiment. In terms of mechanisms, the activation of the TGF-β signaling pathway, indicated by p-smad2/3 activation, is implicated in the progression of NSCLC promoted by WISP3. Additionally, overexpression of WISP3 leads to increased syntenin binding protein (SDCBP) expression in vitro and in vivo, and WISP3 binding to SDCBP enhances angiogenic and tumorigenic potential in NSCLC, which can be counteracted by silencing SDCBP, indicating their crucial role in NSCLC progression. We offer new insights into WISP3's role in promoting NSCLC progression, showing it upregulates SDCBP and is involved in TGF-β signaling. The findings contribute to a better understanding of NSCLC biology and suggest potential therapeutic targets for the disease.