Lkb1 deletion in periosteal mesenchymal progenitors induces osteogenic tumors through mTORC1 activation.

ABSTRACT: Bone osteogenic sarcoma has a poor prognosis as the exact cell of origin and the signaling pathways underling tumor formation remain undefined. Here, we report an osteogenic tumor mouse model based on the conditional knockout of liver kinase b1 (Lkb1; also known as Stk11) in Cathepsin K (Ctsk)-Cre expressing cells. Lineage tracing studies demonstrated that Ctsk-Cre could label a population of periosteal cells. The cells functioned as mesenchymal progenitors with regard to markers and functional properties. LKB1 deficiency increased proliferation and osteoblast differentiation of Ctsk+ periosteal cells, while downregulation of mTORC1 activity, using Raptor genetic mouse model or mTORC1 inhibitor treatment, ameliorated tumor progression of Ctsk-Cre Lkb1fllfl mice. Xenograft mouse models, usi

SUBMITTER: Han Y 

PROVIDER: S-EPMC6486357 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature