Runx2 induces bone osteolysis by transcriptional suppression of TSSC1.
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.
Department of Orthopedics Surgery, The Provincial Hospital Affiliated to Shandong University, Shandong, China.
Da-Chuan
DC
Wang
Hai-Feng
HF
Wang
Ze-Nong
ZN
Yuan
D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology*; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010014:Osteolysis; D015854:Up-Regulation
D050659:Core Binding Factor Alpha 1 Subunit; C109558:EIPR1 protein, human; D009687:Nuclear Proteins; C584163:TSSC1 protein, mouse
Breast cancer; Osteolytic lesions; Runx2; TSSC1