We found that the HCT116 had lost most of the normal colon superenhancer activities but gained a new set of tumor-favoring superenhancers with the critical transcription factors of KLF4, MAZ, MYC, and SMAD3, forming self-rewiring transcriptional regulations that facilitate tumor proliferation, growth signalling, and hypoxia-resistant transcription factors. Here, SMAD3 is linked to neoplasm.