Runx2-Smad signaling impacts the progression of tumor-induced bone disease.

ABSTRACT: Runx2, a master regulator of osteogenesis, is abnormally expressed in advanced prostate cancer. Here, we addressed Runx2 contribution to formation of prostate cancer-related osteolytic and osteoblastic bone lesions by mediating TGFβ/BMP signaling through direct interaction with Smads. Further, we examined involvement of the Runx2-Smad complex in mediating tumor growth and distal metastasis. To identify Runx2-Smad-specific mechanisms of prostate tumor activity in bone, we generated PC3 prostate cancer cell lines expressing Runx2-WT or one of two mutant proteins (Runx2-HTY and Runx2-ΔC) that each disrupt the Runx2-Smad interaction, either directly through a point mutation or by deletion of the functional C-terminus, respectively. Intratibial tumors generated from these cells revealed that Ru

SUBMITTER: Zhang X 

PROVIDER: S-EPMC4289427 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature