Correlation Engine 2.0
Clear Search sequence regions


Sizes of these terms reflect their relevance to your search.

Luminal breast cancer has the highest bone metastasis frequency among all breast cancer subtypes; however, its metastatic mechanism has not been elucidated because of a lack of appropriate models. We have previously developed useful bone metastatic cell lines of luminal breast cancer using MCF7 cells. In this study, we characterized bone metastatic MCF7-BM cell lines and identified c-Jun as a novel bone metastasis marker of luminal breast cancer. The protein level of c-Jun was upregulated in MCF7-BM cells compared with that in parental cells, and its deficiency resulted in the suppression of tumor cell migration, transformation, and reduced osteolytic ability. In vivo, dominant-negative c-Jun exhibited smaller bone metastatic lesions and a lower metastatic frequency. Histologic analysis revealed that c-Jun expression was heterogeneous in bone metastatic lesions, whereas c-Jun overexpression mediated a vicious cycle between MCF7-BM cells and osteoclasts by enhancing calcium-induced migration and releasing the osteoclast activator BMP5. Pharmacological inhibition of c-Jun by the Jun amino-terminal kinase (JNK) inhibitor JNK-IN-8 effectively suppressed tumorigenesis and bone metastasis in MCF7-BM cells. Furthermore, c-Jun downstream signals were specifically correlated with the clinical prognosis of patients with the luminal subtype of breast cancer. Our results illustrate the potential benefits of a therapy that targets c-Jun to prevent bone metastasis in luminal breast cancer. c-Jun expression mediates bone metastasis in luminal breast cancer by forming a vicious cycle in the bone microenvironment, which reveals potential strategies for subtype-specific bone metastasis therapy. ©2023 American Association for Cancer Research.

Citation

Yuxuan Han, Shota Katayama, Mitsuru Futakuchi, Kazuya Nakamichi, Yutaro Wakabayashi, Mai Sakamoto, Jun Nakayama, Kentaro Semba. Targeting c-Jun Is a Potential Therapy for Luminal Breast Cancer Bone Metastasis. Molecular cancer research : MCR. 2023 Sep 01;21(9):908-921

Expand section icon Mesh Tags

Expand section icon Substances


PMID: 37310848

View Full Text