Our results suggest that multicellular-TME enhances CRC malignancy, and this is at least partially mediated by the secretion of TNF-β and TGF-β3, which in turn leads to activation of NF-κB signaling, inducing new cross-talk between stomal cells and HCT116 cells in the CRC TME. The gene discussed is LTA; the disease is colorectal carcinoma.