Thus, our finding uncovered that LUAD cells adapt to TAM2-induced TGF-β enrichment in the tumor microenvironment in two ways: (i) by sensing and activating the canonical TGF-β signaling pathway and (ii) by SE-LINC01977 binding and tethering SMAD3 in the nucleus to promote TGF-β/SMAD3 signaling transduction via epigenetic regulation. This evidence concerns the gene SMAD3 and neoplasm.