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. Author manuscript; available in PMC: 2025 Jul 1.
Published in final edited form as: Nature. 2024 Aug 7;633(8029):451–458. doi: 10.1038/s41586-024-07787-1

Extended Data Figure 4. Sphingolipid abundance mediates tumor control.

Extended Data Figure 4.

a. Schematic of the sphingolipid metabolism focused CRISPR screen. Syngeneic cancer cell lines derived from C57BL/6J mice were transduced with the sphingolipid metabolism library and injected subcutaneously (SQ) into the flanks of C57BL/6J (B6) or NSG mice. Tumors were collected, their genomic DNA extracted, and guide RNA (sgRNA) abundance was determined. N ≥ 3 mice/ group.

b. Immunoblot analysis of Sptlc1 and Sptlc2 in HY15549 cells overexpressing empty vectors or Sptlc1 and Sptlc2 cDNA. Gapdh is used as a loading control.

c. Volcano plot showing log2 fold difference in ceramide-derived lipid species between double-empty vector wildtype (dEV) or Sptlc1/Sptlc2 double-overexpression (dOE) HY15549 cells.

d. Weights (top) and image (bottom) of double-empty vector wildtype (dEV) or Sptlc1/Sptlc2 double-overexpression (Sptlc1/2_dOE) HY15549 tumors grown in NSG mice. Mean ± SEM, n = 6 mice/ group, scale bar = 1 cm.

e. Progression (left) and disease (right) free survival analysis of TCGA PDAC patients with high (blue) or low (pink) expression of SPTLC1, SPTLC2, and KDSR. N = 177. Error bands = 95% confidence interval.