Runx2 induces bone osteolysis by transcriptional suppression of TSSC1

• Published in: Biochemical and biophysical research communications Vol. 438; no. 4; pp. 635 - 639
• Main Authors: Wang, Da-Chuan, Wang, Hai-Feng, Yuan, Ze-Nong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.09.2013
• Subjects: Animals; Bone and Bones - metabolism; Bone and Bones - pathology; Bone Neoplasms - genetics; Bone Neoplasms - metabolism; Bone Neoplasms - pathology; Bone Neoplasms - secondary; Breast - metabolism; Breast - pathology; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Line, Tumor; Core Binding Factor Alpha 1 Subunit - genetics; Core Binding Factor Alpha 1 Subunit - metabolism; Female; Gene Expression Regulation, Neoplastic; Humans; Mice; Mice, SCID; Neoplasm Invasiveness - genetics; Neoplasm Invasiveness - pathology; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Osteolysis; Osteolytic lesions; Runx2; TSSC1; Up-Regulation; Breast cancer; TSSC1; Osteolytic lesions; Runx2
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2013.07.131

•Overexpression of TSSC1 inhibits breast cancer metastasis.•Runx2 transcriptionally down-regulated TSSC1 expression.•Runx2 promotes breast cancer metastasis by down-regulation of TSSC1.•Runx2 mediates breast cancer-induced osteolytic bone disease in a TSSC-dependent manner. Advanced breast cancers frequently metastasize to bone, resulting in osteolytic lesions, however, the underlying mechanisms are poorly understood. Runx2, a bone-specific transcriptional factor, is abnormally expressed in highly metastatic breast cancer cells. Here, we found that TSSC1 inhibits breast cancer cell invasion. Subsequently, TSSC1 is confirmed as a target of Runx2 and is negatively regulated by Runx2. Furthermore, overexpression of Runx2 induces bone osteolysis in a TSSC1-dependent manner. Our results may provide a strategy for the treatment of breast cancer and the prevention of skeletal metastasis.