Fig. 6

Schematic representation of the LSS-triggered VEGF-ATOH8 signal axis mediates CRC m-CTCs survival. The exposure of 4–20 dyn/cm² LSS can upregulate ATOH8 expression by promoting autocrine VEGF secretion of colorectal cancer cells in the circulation. These ATOH8_high m-CTCs possess an advantage in surviving and establishing distant metastases. Mechanically, in CRC m-CTCs responding to LSS stimulation, VEGF activates the downstream AKT pathway by acting on the VEGFR2 receptor, thereby facilitating ATOH8 expression. Meanwhile, ATOH8 advances HK2 transcription, which not only enhances the mitochondrial binding of HK2 to VDAC, but also inhibits ROS production through activating glycolysis. Both ultimately contribute to the survival of CRC m-CTCs