Quantitative proteomics identify Tenascin-C as a promoter of lung cancer progression and contributor to a signature prognostic of patient survival

摘要: The extracellular microenvironment is an integral component of normal and diseased tissues that poorly understood owing to its complexity. To investigate the contribution lung fibrosis adenocarcinoma progression, two pathologies characterized by excessive stromal expansion, we used mouse models characterize matrix (ECM) composition lung, fibrotic tumors, metastases. Using quantitative proteomics, identified assayed abundance 113 ECM proteins, which revealed robust protein signatures unique fibrosis, primary or These analyses indicated significantly increased several S100 including Fibronectin Tenascin-C (Tnc), in tumors associated lymph node metastases compared with tissue. We further showed Tnc expression repressed transcription factor Nkx2-1, a well-established suppressor metastatic progression. found increasing levels Tnc, via CRISPR-mediated transcriptional activation endogenous gene, enhanced dissemination cells. Interrogation human cancer gene data high TNC correlates worse prognosis for adenocarcinoma, three-gene signature comprising TNC, S100A10, S100A11 predictor patient survival independent age, sex, smoking history, mutational load. Our findings suggest tumor underexplored source diagnostic markers potential therapeutic targets patients.