ICAM1 promotes bone metastasis via integrin‐mediated TGF‐β/EMT signaling in triple‐negative breast cancer

Bone‐related events caused by breast cancer bone metastasis substantially compromise the survival and quality of life of patients. Because triple‐negative breast cancer (TNBC) lacks hormone receptors and Her2‐targeted therapeutic options, progress in the treatment of TNBC bone metastasis has been very slow. Intercellular adhesion molecule 1 (ICAM1) is highly expressed in various cancers and plays an important role in tumorigenesis and metastasis. However, the effect and mechanism of ICAM1 in TNBC bone metastasis are still unknown. We found that ICAM1 was highly expressed in TNBC and correlated with prognosis in TNBC patients. Cell lines with high expression of ICAM1 exhibited enhanced bone metastasis in tumor‐bearing mice, and silencing ICAM1 expression significantly inhibited bone metastasis in mice. ICAM1 interacted with integrins to activate the epithelial‐to‐mesenchymal transition program through TGF‐β/SMAD signaling, ultimately enhancing cell invasiveness. Therefore, the findings of the present study provide a strong rationale for the application of ICAM1‐targeted therapy in TNBC patients with bone metastasis. ICAM1 promoted TNBC bone metastasis in TNBC. ICAM1 initialed EMT in TNBC cells. ICAM1 activated TGF‐β/SMAD signaling. " cd_value_code="text