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. 2016 Oct 12;7(46):76062–76075. doi: 10.18632/oncotarget.12584

Figure 7. Proposed Mechanism of Gli2 Mediated Bone Destruction in OSCC.

Figure 7

OSCC signals through several signaling pathways to increase PTHrP. Canonical Hh signaling activates Gli2 protein accumulation and increases Gli2 expression, both of which can increase PTHrP expression. TGFβ signaling increases Smad2/3 activation, which increases Gli2 expression. Increased p38/MAPK activity can also increase Gli2 levels by stabilizing Gli2 protein. B-catenin activation increases Gli2 expression and directly and may also indirectly affect Gli2 protein levels through cross-talk. Gli2 increases PTHrP expression in OSCC, which results in an increase in osteoblast-mediated (through RANKL/RANK) osteoclast activation, resulting in increased bone resorption.