Mechanistically, K3 overexpressing cells showed a marked increase in VEGF production, which was attributed to enhanced expression of the transcription factor Twist and enhanced β1 integrin activation.[104] In vivo, K3 overexpression in a breast cancer cell line increased primary tumor growth and lung metastasis, a consequence of enhanced tumor angiogenesis consistent with increased VEGF production and macrophage recruitment, downstream of Twist, which also activates the EMT program [104]. This evidence concerns the gene TWIST1 and breast cancer.