Cancers can develop through epigenetic pathways even without driver gene mutations (DGMs), according to a study from Science Tokyo. Researchers uncovered the YAP1–TEAD–TET1 axis, which triggers DNA demethylation and activates multiple oncogenes in hepatocellular carcinoma. Suppressing TET1 reduced tumor formation in mice, while analysis of human liver disease data supported the relevance of these findings. This study reveals an alternative epigenetic route to cancer development and offers new insights into DGM-negative cancers.

After shedding from the primary lesion, disseminated cancer cells invade into tumor stroma and intravasate into the nearby vasculature. While most of circulating tumor cells become apoptotic due to the harsh microenvironment within the vasculature, a small subpopulation of them still survives and extravasates for the generation of secondary lesions in distant organs, which account for more than 90% of cancer-related death. During this metastatic journey, cancer cells encounter distinct mechanical stimuli, such as geometric confinement, hydraulic resistance, and fluid shear stress, which considerably affect the survival and malignant functions of these disseminated tumor cells and thus the metastatic inefficiency. This review summarizes the latest findings of how these mechanical cues modulate the fate of cancer cells from intravasation to extravasation, highlighting the importance of mechano-regulation during cancer metastasis.