Fig. 8: Targeting HSC TUFT1 by Cre/LoxP recombination suppresses HSC activation and CRCLM in mice. | Cell Death & Differentiation

Fig. 8: Targeting HSC TUFT1 by Cre/LoxP recombination suppresses HSC activation and CRCLM in mice.

From: TUFT1 stabilizes TGF-β receptor II protein and facilitates activation of hepatic stellate cells into metastasis-promoting myofibroblasts

Fig. 8

A A schematic representation of the study to generate CRCLM in control and conditional TUFT1 knockout mice. B, C Mice were sacrificed at day 15 after portal vein injection of MC38 CRC cells. Representative pictures of murine livers at the endpoint are shown in (B), and the weight of MC38 CRCLM is shown in (C). ***P < 0.001 by t-test, n = 7. D α-SMA IF revealed that the CAF density of MC38 liver metastasis (LM) was lower in TUFT1flox/floxCol1a2-CreER mice than in TUFT1flox/flox mice. Scale bar, 50 μm. ***P < 0.001 by t-test, n = 7. E WB detected that the levels of 4 tumor-promoting factors were all reduced in MC38 LM of TUFT1flox/floxCol1a2-CreER mice compared to those of TUFT1flox/flox mice. **P < 0.01, ***P < 0.001 by t-test, n = 7. F Double IF for α-SMA and TUFT1 demonstrated much reduced TUFT1 IF in TUFT1flox/floxCol1a2-CreER CAFs compared to TUFT1flox/flox CAFs of the MC38 LM. Scale bar, 25 μm. ***P < 0.001 by t-test, n = 28, 21. G A diagram summarizing the mechanism by which TUFT1 of HSCs protects TβRII from degradation in HSCs and facilitates TGF-β1-mediated activation of HSCs into CAFs that promote CRCLM.

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