However, these opposite effects of Reo administration on TGF-β production and the expression of TGF-β target genes may not necessarily involve the canonical TGF-β signaling pathway, because MC38 tumor cells lack Smad4-mediated responses and the expression of many TGF-β target genes can also be induced or inhibited by other pathways. The gene discussed is TGFB1; the disease is neoplasm.