Overall, our findings support that ICAM1 plays a key role in the initiation of metastasis by: (i) mediating tumor cell aggregation through homotypic ICAM1-ICAM1 interactions for CTC cluster formation; (ii) enhancing stemness by upregulating stemness-related genes; (iii) enhancing tumor cell-endothelial cell cross-talk through heterotypic ICAM1-ICAM1 interactions, which promote TEM; and (iv) promoting tumor cell proliferation through sustaining or activating downstream CDK6. This evidence concerns the gene CDK6 and neoplasm.