Fig. 9

The important role of PD-L1 in EFEMP2 promoting EMT progression and the inhibitory effect of EFEMP2 knockdown on the abdominal dissemination of ovarian cancer cells in nude mice. a PD-L1 knockout significantly increased the levels of E-cadherin, while down-regulated the levels of N-cadherin, vimentin, Slug, Snail and Zeb1, indicating that downregulation of PD-L1 inhibited EMT process. b Up-regulation of PD-L1 induced EMT, accompanied by decreased E-cadherin levels, and increased N-cadherin, vimentin, Slug, Snail and Zeb1 levels. c Downregulated PD-L1 significantly inhibited the EMT process induced by EFEMP2 overexpression, accompanied by an increase in E-cadherin level, and decreased levels of N-cadherin, vimentin, Slug, Snail and Zeb1. d However, overexpressed PD-L1 restored the EMT process that had been hampered by EFEMP2 knockout. e EFEMP2 down-expression could significantly inhibit the spread of ovarian cancer cells in the abdominal cavity of nude mice, but the overexpression of PD-L1 drastically promoted the process. f The therapeutic effect of Trametinib in inhibiting abdominal spread of ES-2 NC, EFEMP2 shRNA infected cells and EFEMP2 shRNA and PD-L1 cDNA co-transfected cells. g The therapeutic effect of Afatinib in inhibiting abdominal spread of ES-2 NC, EFEMP2 shRNA infected cells and EFEMP2 shRNA and PD-L1 cDNA co-transfected cells. h Effect of Trametinib and Afatinib combination therapy in inhibiting abdominal spread of ovarian cancer cells. i EFEMP2 could induce PD-L1 regulation in ovarian cancer cells by activating the EGFR/ERK1/2/c-Jun pathway rather than the JNK/c-Jun pathway