CtBP1/2 KD increased the metabolic stress and DNA replication instability, and could activate HIPK2, a serine /threonine kinase in the TGF-β signaling pathway, by checkpoint kinase ATM under stress and leading to apoptosis in cancer cells, which directly or indirectly (via JNK1) phosphorylates the sites of Ser422 and Ser428 in CtBP1 and CtBP2 [36–38], respectively. This evidence concerns the gene TGFB1 and cancer.