Metastasis is responsible for the majority of breast cancer-related deaths. The metastatic spread of cancer cells is a complicated process that requires considerable flexibility in the adhesive properties of both tumor cells and other interacting cells. Cell adhesion molecules (CAMs) are membrane receptors that mediate cell-cell and cell-matrix interactions, and are essential for transducing intracellular signals responsible for adhesion, migration, invasion, angiogensis, and organ-specific metastasis. This review will discuss the recent advances in our understanding on the biological functions, signaling mechanisms, and therapeutic potentials of important CAMs involved in breast cancer metastasis.

Bone metastasis affects more than 70% of advanced breast cancer patients, but the molecular mechanisms of this process remain unclear. Here, we present clinical and experimental evidence to clarify the role of the integrin b-like 1 (ITGBL1) as a key contributor to bone metastasis of breast cancer. In an in vivo model system and in vitro experiments, ITGBL1 expression promoted formation of osteomimetic breast cancers, facilitating recruitment, residence, and growth of cancer cells in bone microenvironment along with osteoclast maturation there to form osteolytic lesions. Mechanistic investigations identified the TGFb signaling pathway as a downstream effector of ITGBL1 and the transcription factor Runx2 as an upstream activator of ITGBL1 expression. In support of these findings, we also found that ITGBL1 was an essential mediator of Runx2-induced bone metastasis of breast cancer. Overall, our results illuminate how bone metastasis occurs in breast cancer, and they provide functional evidence for new candidate biomarkers and therapeutic targets to identify risk, to prevent, and to treat this dismal feature of advanced breast cancer.