By using a 3D organoid co-culture model, the authors found that the TNF-α secreted by cancer cells induces the upregulation of TGF-α in CAFs via the NF-κB signaling pathway; thereafter, CAF-derived TGF-α enhances the colony forming ability of metastatic cancer cells through the activation of EGFR, AKT, and ERK1/2 signaling. The gene discussed is AKT1; the disease is cancer.