Figure 1.

HIC‐5 in metastasis regulation and tumor invasion; potential mechanistic links to oncogene‐induced senescence. In senescence induced by the BRAF or RAS oncogenes, tissue remodeling is dependent on the induction of SASP proteins by mtROS, generated by NOX4. Mori et al. propose a novel pathway to regulate NOX4 expression and mtROS. It involves the adaptor protein HIC‐5 and the matrix metalloprotease MMP9 and is supposed to affect the metastatic properties of tumor epithelial cells transformed by the RAS oncogene. In their model, HIC‐5 acts as a ROS sensor via its oxidation sensitive NES. Generation of ROS is triggered after detachment of cells from the extracellular matrix (matrix detachment), a required step in metastasis. The increase of nuclear HIC‐5 results in activation of its pleotropic function as an adaptor protein to regulate transcription. The role if any of HIC‐5 in oncogene‐induced senescence remains elusive.