Alteration of E-cadherin protein level during epithelial-mesenchymal transition (EMT) or mesenchymal-epithelial transition (MET) plays important role in cancer metastasis (1). In a recent paper “Liver Protects Metastatic Prostate Cancer From Induced Death by Activating E-cadherin Signaling” by Ma et al. (2) reported that the interaction between liver cells and metastatic prostate cancer (PCa) cells provokes re-expression of E-cadherin in PCa cells, which protects PCa cells from cell death induced by chemotherapeutic drugs. E-cadherin fabricates this protection via activation of canonical survival signaling pathways, including the extracellular signal-regulated kinases (ERK), protein kinase B (AKT), and the Janus kinase (JAK) signaling. Ma et al. used DU-145, an androgen-receptor (AR)-negative androgen-independent PCa cell line which expresses very low level of E-cadherin on the cell membrane to determine the role of E-cadherin in PCa chemotherapy resistance. The researchers found that either co-culture with primary hepatocytes to mimic liver cell microenvironment or addition of PD153035 (inhibitor suppressing the kinase activity of epidermal growth factor receptor, EGFR) induced the re-expression of E-cadherin in DU-145. These E-cadherin-high DU-145 cells were much more resistant to chemotherapeutic drugs treatment and TNF-related apoptosis-inducing ligand (TRAIL) both in vitro and in vivo.
Date:
2016-12
Relation:
Translational Andrology and Urology. 2016 Dec;5(6):961-963.
