Fig. 5: PKM2 nuclear translocation promotes glycolytic reprogramming of CAFs and affects DNA loss repair in PDAC cells.

A, B The relative mRNA levels of c-Myc, GLUT1 and LDHA were measured by qPCR in CAFs cells transfected with empty vector, circABCC4, lenti-NC-shRNA, or lenti- NC-shRNA, or lenti-circABCC4-shRNA. C, D The lactate levels in CAFs transfected with empty vector, circABCC4, lenti-NC-shRNA, or lenti-circABCC4-shRNA were quantified. E Cytokine antibody array of conditional medium from CAFs transfected with lenti-NC-shRNA, or lenti-circABCC4-shRNA. F–H IL-8 mRNA expression determined by qPCR from CAFs transfected with empty vector or circABCC4, and then added with glucose, lactate (G) or 2-DG (H). I Imaging and quantification of oxaliplatin-induced DNA damage using a neutral comet assay from Panc-1 after coculturing with CAFs transfected with empty vector, circABCC4, lenti-NC-shRNA, or lenti-circABCC4-shRNA. Scale bar, 200 μm. J Imaging and quantification of γH2AX-positive foci from Panc-1 after coculturing with CAFs transfected with empty vector, circABCC4, lenti-NC-shRNA, or lenti-circABCC4-shRNA. Scale bar, 5 μm. K Imaging and quantification of oxaliplatin-induced DNA damage using a neutral comet assay from Panc-1 after coculturing with CAFs treated with 2-DG, Scale bar, 200 μm. L Imaging and quantification of γH2AX-positive foci from Panc-1 after coculturing with CAFs treated with 2-DG. Scale bar, 5 μm. M Imaging and quantification of oxaliplatin-induced DNA damage using a neutral comet assay from Panc-1 after coculturing with CAFs treated with shikonin, Scale bar, 200 μm. N Imaging and quantification of γH2AX-positive foci from Panc-1 after coculturing with CAFs treated with shikonin. Scale bar, 5 μm.