Notch signal activation results in the transcription of HES/HEY network. These factors are multi-functional in terms of angiogenesis, metastatic niche formation by ECM remodeling.
For instance, activated Notch signal pathway in breast cancer cells in the pre-metastatic niche induces the production and secretion of IL-6, which affects the bone remodeling by influencing differentiation and activation of osteoclasts in comparison with osteoblasts. The abnormal bone remodeling lets the potentially metastasized breast cancer cells colonize and proliferate in the bone marrow.