Non‐small‐cell lung cancer (NSCLC) accounts for one of the most deadly cancers due to metastasis after therapy. Cancer metastasis usually results from epithelial‐to‐mesenchymal transition (EMT), and metabolic disorder is a key mediator of lung cancer EMT. The linkage between metabolic disorder and NSCLC EMT is still unclear. Using in silico analysis, C4ST1, a key enzyme of glycosaminoglycan synthesis pathway was up-regulation in mesenchymal type NSCLC cells. C4ST1 catalyzes chondroitin sulfate A (CsA) formation. We found both C4ST1 and CsA were up-regulation in mesenchymal type NSCLC cells. Not only C4ST1 overexpression but also CsA treatments changed NSCLC EMT balance and decreased the transcriptional activity on CDH1 promoter region. Furthermore, both treatments could promote in vitro NSCLC migration and invasion abilities in the epithelial type NSCLC cells. Up-regulation of C4ST1 cells also promoted lung cancer metastasis. Moreover, we used CsA binding peptide as a targeting ligands of metastatic NSCLC cells on theranostics nanoparticles. In summary, this study finds key gene in NSCLC EMT. Up-regulation of C4ST1 promotes NSCLC EMT and cell surface CsA content which may provide a novel theranostics niche on metastatic NSCLC cells.

Citation Format: LI-JIE LI, Ming-Hsien Chan, Wei-Min Chang, Michael Hsiao. Theranostics nanoparticles targeting to metastatic non small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2883.