Fig. 7

ANXA1 Mediates RRM2-Induced Activation of AKT and Docetaxel Resistance in Prostate Cancer. A RRM 2 knockdown significantly inhibited the phosphorylation of AKT in diseased tissue, while improving the therapeutic effect of docetaxel, and overexpression of ANXA 1 enhanced the phosphorylation of AKT. ANXA 1 silencing inhibited RRM 2 changes, which in turn affects AKT phosphorylation and drug sensitivity. B Expression of ANXA1 increases in LNCaP and 22Rv1 cells upon treatment with increasing concentrations of docetaxel within a certain range. ANXA1 level is obviously higher in docetaxel-resistant tumour group compared to that in sensitive group. C The docetaxel resistance induced by RRM2 suppression is largely reversed by ANXA1 overexpression in prostate cancer cells. D–F RRM2 knockdown decreases the protein level of ANXA1, shortens its half-life, and increases its ubiquitination level without affecting its mRNA level. G UBE3A knockout promotes the protein expression of ANXA1 in PC3 cells, which reflected that UBE3A plays a role in ANXA1 degradation. H–I The ANXA1 protein level is positively correlated with the RRM2 level in PCA tissues