BoneKEy Reports | BoneKEy Watch
BACH1, a novel master regulator of metastasis from breast to bone
In the past few years several individual genes that contribute to metastasis from primary breast cancers have been discovered; in this study, Liang et al. set out to identify master regulators of those genes.
Using reverse engineering followed by experimental validation, the authors confirmed that both Smad4 and HIF1 act as regulators of metastasis from breast tissue to bone. They also picked up on a novel master regulator, BACH1, showing that this regulates several genes involved in metastasis of breast cancer to bone, particularly MMP1 and CXCR4, which both enhance the ability of the cells to migrate and invade distant sites.
Depleting BACH1 in a mouse model of bone metastasis significantly reduced metastasis, while enhanced ectopic expression of the gene made cancer cells more malignant and aggressive. Studies in human datasets showed that expression of BACH1 and its related genes consistently predicted bone metastasis and patient deaths. The findings have therapeutic implications and also provide a proof-of-concept for this approach, which could be used to identify key controller genes in other diseases.
Editor's comment: This study identifies transcription factor BACH1 as a regulator of metastasis-associated genes, including MMP1 and CXCR4, which are critical for bone metastasis formation. BACH1 may therefore be an important target for therapeutic intervention.
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