Fig. 5 | Nature Communications

Fig. 5

From: An inflammatory-CCRK circuitry drives mTORC1-dependent metabolic and immunosuppressive reprogramming in obesity-associated hepatocellular carcinoma

Fig. 5

Hepatic CCRK promotes lipid accumulation, glucose uptake, insulin resistance, and tumorigenicity through mTORC1 activation. a Doxycycline (Dox)-induced expression of CCRK-activated mTORC1 signaling pathway in LO2-CCRK cells, which was abolished by inhibition of mTOR via Raptor knockdown or treatment with Rapamycin (Rapa). b, c Lipid accumulation (image magnification =×400, scale bar = 20 μm) as well as d glucose uptake were increased by CCRK-mediated mTOR activation, but were reduced by mTORC1 inhibition. e mTORC1 signaling was suppressed in CCRK KO Huh7 cell line. f CCRK impaired insulin sensitivity in Huh7 cells, which was restored by CCRK KO. Insulin sensitivity was assessed by p-AktSer473 expression via Western blot analysis in cells treated with high dose of insulin followed by low dose of insulin stimulation. g The CCRK-induced insulin intolerance was restored by inhibition of mTORC1 using shRaptor or Rapamycin. h, i Mice injected with Dox-induced LO2-CCRK cells developed larger tumors (scale bar = 1 cm) compared to control mice and those treated with shRaptor or Rapamycin (n = 5 per group). j, k CCRK promoted tumorigenicity through mTORC1 activation. j The cell proliferation was assessed by Ki67 staining (scale bar = 20 μm). k The CCRK-activated mTORC1 signaling was detected by Western blot analysis. Data are presented as mean ± SD. *p < 0.05; **p < 0.01; and ***p < 0.001 as calculated by one-way ANOVA followed by Bonferroni post-hoc test (b, d, i, j), and two-way ANOVA followed by Bonferroni post-hoc test (h)

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