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. Author manuscript; available in PMC: 2019 Oct 1.
Published in final edited form as: Endocr Relat Cancer. 2018 Jun 18;25(10):865–877. doi: 10.1530/ERC-18-0071

Figure 5. A proposed model to account for the actions by which metformin and JQ1 together inhibit tumor progression in HFD-ThrbPV/PV Pten+/− mice.

Figure 5

HFD induces the aberrant activation of STAT3 and ERK signaling to promote thyroid cancer progression in HFD-ThrbPV/PV Pten+/− mice. JQ1 and metformin together act to increase the tumor cell apoptosis by elevating the protein levels of pro-apoptotic regulators Bim and BAD and by suppressing the protein levels of anti-apoptotic regulators (Mcl1, Bcl2 and survivin), resulting in increased cleaved caspase 3 activity. Combined treatment of JQ1 and metformin also act to suppress invasion and metastasis by decreasing EMT key regulators (cMyc, MMP9, fibronectin, vimentin, N-cadherin) and increasing E-cadherin protein levels. By acting on these two pathways, JQ1 and metformin together suppress obesity-activated thyroid cancer progression. The extent in the thickness of the lines in the inhibition of pSTAT3 and pERK signaling schematically represents the degree of suppression.