Fig. 4

CLDN6 inhibits HIF-1α deSUMOylation by downregulating SENP1. a SENP1 mRNA and protein levels in CLDN6-overexpressing breast cancer cells. b SENP1 mRNA and protein levels in CLDN6-KO HBL-100 cells. c SENP1 overexpression in MDA-MB-231/CLDN6 cells restored the expression of HIF-1α. d GSEA plots of the Protein Modification by Small Protein Conjunction Or Removal pathway analysed according to SENP1 (left) or CLDN6 (right) expression. e Comparison of SUMO1-HIF-1α binding levels between CLDN6-overexpressing and CLDN6/SENP1-overexpressing MDA-MB-231 cells. Cells were treated with proteasome inhibitor MG-132, so that there was the same amount of background HIF-1α expression. f Map of the SUMOylation site mutant HIF-1α plasmid. g WB analysis indicating that CLDN6 downregulated WT but not MUT HIF-1α expression. h Mutation of the SUMOylation sites in HIF-1α rescued the loss of metastasis in CLDN6-overexpressing breast cancer cells. Scale: 50um. * p < 0.05