In hESCs and other types of cancer cells, Nodal regulates target gene transcription by phosphorylating heterodimeric complexes of type I (ALK4/7) and type II (ActRIIB) activin-like kinase receptors followed by the ALK 4/7–mediated phosphorylation of Smad2/3, with or without the Smad4 phosphorylation [34], and translocates into the nucleus [2, 9, 12]. This evidence concerns the gene SMAD4 and cancer.