While our data strongly support a role for ZO-1 as a negative regulator of tumor angiogenesis, further studies are warranted to determine whether inhibition of IL-8 or KLF5 can reverse the angiogenic phenotype in ZO-1–deficient cells, and whether ZO-1 loss contributes to tumor progression and metastasis in vivo. This evidence concerns the gene CXCL8 and neoplasm.