Gene expression network in cancer cells is orchestrated by a small number of master regulator transcription factors (MRTFs), which play a prominent role in regulating cancer intrinsic hallmarks, such as sustaining proliferative signaling, evading growth suppressors, resisting cell death, etc. A new study reports a new role of one MRTF, KLF5, in regulating tumor microenvironment in an extrinsic manner. This evidence concerns the gene KLF5 and cancer.