NUPR1 and cancer: At the present, we do not know how important Nupr1 is in TRCs in many other carcinomas, but the abrogation of the inhibitory role of Nupr1 in soft matrices and the upregulation of Nupr1 in stiff matrices support the postulate of physical microenvironment barrier in cancer progression26 and are consistent with the role of 3D stiff matrices in inhibiting carcinoma progression.3 In the future, we need to determine how Nupr1, together with other tumor suppressors, inhibits carcinoma progression in human subjects and to find ways to perturb this pathway to stop cancer progression.