ITGBL1 is a Runx2 Transcriptional Target and Promotes Breast Cancer Bone Metastasis by Activating the TGF-β Signaling Pathway
Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, en activant la voie de signalisation TGF-bêta, la protéine ITGBL1 favorise la formation de métastases osseuses d'une tumeur du sein
Bone metastasis affects over 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 β-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 TGF-β 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, prevent and treat this dismal feature of advanced breast cancer.