Fig. 6 | Nature Communications

Fig. 6

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

Fig. 6

Hepatic CCRK-mTORC1 signaling recruits MDSCs to form a tumor-prone liver microenvironment. a mTORC1 signaling was activated in the livers of CCRK TG mice. The downstream molecules of mTORC1 signaling were detected by Western blot. b mTORC1 signaling components were activated in the primary hepatocytes isolated from CCRK TG mice. c Schematic diagram of CCRK TG mouse model with intrahepatic injection of Ccrk KO Hepa1–6 cells by CRISPR/Cas9, and lentiviral-mediated Raptor knockdown. d CCRK TG mice (n = 8) developed significantly larger tumors compared to controls (n = 11), which was abolished by down-regulation of Raptor (shRaptor; n = 5) (scale bar = 1 cm). e PMN-MDSCs were induced in CCRK TG mice, but were reduced after Raptor knockdown, and f PMN-MDSC levels positively correlated with tumor weight. g PMN-MDSCs were induced by HFHC diet, but were reduced by Ccrk knockdown in NASH-HCC model (CD+shCtrl, n = 8; HFHC+shCtrl, n = 15; HFHC+shCcrk, n = 15), wherein h PMN-MDSC levels positively correlated with tumor multiplicity. i G-csf mRNA levels were induced by HFHC diet, but were reduced by Ccrk knockdown in NASH-HCC model. j G-CSF mRNA level was augmented by CCRK over-expression in LO2 cells, which could be attenuated by Raptor knockdown. k G-CSF mRNA expression was down-regulated in CCRK KO Huh7 cells. Data are presented as mean ± SD. *p < 0.05 and **p < 0.01 as calculated by one-way ANOVA followed by Bonferroni post hoc test (d, e, g, i, j), Pearson correlation (f, h), and unpaired two-tailed Student’s t-test (k)

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