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. Author manuscript; available in PMC: 2015 Dec 1.
Published in final edited form as: Clin Exp Metastasis. 2014 Oct 31;31(8):945–959. doi: 10.1007/s10585-014-9682-1

Figure 8. Wnt induces Gli2 and PTHrP in osteolytic tumor cells.

Figure 8

Tumor cells (green) in the bone microenvironment sense the rigidity of the bone (gray) via mechanotransduction (lightning bolts), which induces Wnt signaling and an accumulation of nuclear B-catenin in tumor cells. This drives the transcription of Gli2 and PTHrP and facilitates tumor cell growth in the bone. Additionally, bone marrow stromal cells (BMSCs, purple) secrete Wnt ligands (including Wnt3a) that drive Gli2 and PTHrP transcription in disseminated tumor cells. Wnt signaling induction of Gli2 transcription is dependent upon downstream TGF-β signaling molecules Smads 2 and 3. TGF-β = transforming growth factor-beta, BMSC = bone marrow stromal cells.