Fig. 4: Prophylactic or therapeutic Atf6 targeting reduces HCC.
From: Activated ATF6α is a hepatic tumour driver restricting immunosurveillance
a, Schematic and liver images of DEN/HFD-treated Atf6+/+ and Atf6−/− mice. Scale bar, 1 cm. b,c, The tumour incidence (b), number (c; left) and area (c; right, cm2) of DEN/HFD-treated Atf6+/+ and Atf6−/− mice. d, Representative liver H&E staining of DEN/HFD-treated Atf6+/+ and Atf6−/− mice. Scale bar, 3 mm. e, Representative liver TEM images of DEN/HFD-treated Atf6+/+ and Atf6−/− mice. Scale bar, 1 µm. Quantification is shown in Extended Data Fig. 7h. Gly, glycogen. f, GSEA27 of liver tumour RNA-seq data from DEN/HFD-treated Atf6+/+ and Atf6−/− mice. g, Schematic and liver images of CD-HFD-fed Atf6fl/fl and Atf6ΔHep mice. Scale bar, 1 cm. h,i, The tumour incidence (h), number and area (i; cm2) of CD-HFD-fed Atf6fl/fl and Atf6ΔHep mice. j, Representative liver H&E staining of CD-HFD-fed Atf6fl/fl and Atf6ΔHep mice. Scale bar, 3 mm. k, Volcano plot of liver RNA-seq data from Atf6ΔHep versus Atf6fl/fl mice. l, Liquid chromatography–mass spectrometry (LC–MS) analysis of hepatic glucose in Atf6fl/fl and Atf6ΔHep mice. m, Schematic and liver images of Atf6+/+ and Atf6−/− mice crossed with MUP-uPA mice and fed a HFD. Scale bar, 1 cm. n, The tumour number (left) and area (right; cm2) of Atf6+/+:MUP-uPA and Atf6−/−:MUP-uPA mice. o, Representative liver H&E staining of HFD-fed Atf6+/+:MUP-uPA and Atf6−/−:MUP-uPA mice. Scale bar, 3 mm. p, Schematic and liver images of MUP-uPA mice administered GalNac-ASO-scramble or GalNac-ASO-Atf6. Scale bar, 1 cm. q, Representative liver TEM images of ASO-scramble- or ASO-Atf6-treated MUP-uPA mice. Scale bar, 500 nm. Quantification is shown in Extended Data Fig. 8f. C, collagen. r, Representative liver PAS staining and IHC for BiP and CHOP in ASO-scramble- or ASO-Atf6-treated MUP-uPA mice. Scale bar, 200 µm. Quantification is shown in Extended Data Fig. 8e. s, Schematic and liver images of HFD-fed MUP-uPA mice administered GalNac-ASO-scramble or GalNac-ASO-Atf6. Scale bar, 1 cm. t, The tumour number (left) and area (right) of 30-week-old untreated or 40-week-old ASO-scramble- or ASO-Atf6-treated MUP-uPA mice. u, Representative liver H&E staining of ASO-scramble- or ASO-Atf6-treated MUP-uPA mice. Scale bar, 3 mm. v, Schematic and liver images of GalNac-ASO-scramble- or GalNac-ASO-Atf6-treated C57BL/6J + NRASG12V mice. Scale bar, 1 cm. w, Tumour area (cm2) of ASO-scramble- or ASO-Atf6-treated C57BL/6J + NRASG12V mice. x, Representative liver H&E staining of ASO-scramble- or ASO-Atf6-treated C57BL/6J + NRASG12V mice. Scale bar, 3 mm. The sample sizes, biological replicates and statistical tests are described in the Methods and Source data.
