On the one hand, VEGF and other factors secreted by tumor cells can down‐regulate the tight junction proteins between endothelial cells, such as Claudin‐5 and Occludin, so that the expression of these proteins can be reduced, thus destroying the structure of endothelial cell tight junction.[79] At the same time, ZO‐1 as a scaffolding protein of the tight junctions may be displaced and dysfunctional due to tumor‐related factors, resulting in the down‐regulation of its normal tight junction function and impairment of the integrity of the BBB. The gene discussed is VEGFA; the disease is neoplasm.