Castrate resistant prostate cancer (CRPC) accounts for almost all prostate cancer (PCa) deaths. Aberrant activation of ERK/MEK and PI3K/AKT signaling pathways plays an important role in subsets of patients with CRPC. The role of protocadherin 7 (PCDH7) in modulating these signaling pathways is investigated for the first time in PCa in the present investigation.
PCDH7 expression was analyzed in CRPC/neuroendocrine prostate cancer (NEPC) dataset. Protein expression was assessed by Western blotting and immunohistochemistry, and messenger RNA (mRNA) by quantitative real-time polymerase chain reaction. Small hairpin ribonucleic acid was used to knockdown PCDH7. Colony formation, cell migration, and invasion studies were done using standard protocols.
PCDH7 amplification/mRNA upregulation was observed in 41% of patients in CRPC/NEPC dataset. PCDH7 was also overexpressed in CRPC cells. Increased PCDH protein expression was observed during tumor progression in PCa tissues and in TRAMP mice. Epidermal growth factor treatment resulted in aberrant activation of ERK/AKT. Knockdown of PCDH7 decreased ERK, AKT, and RB phosphorylation and reduced colony formation, decreased cell invasion, and cell migration.
These data show for the first time that PCDH7 is overexpressed in a large number of patients with CRPC and suggest that PCDH7 may be an attractive target in subsets of patients with CRPC for whom there is no cure to-date.
The Prostate. 2019 Aug 26 [Epub ahead of print]
Gauri Shishodia, Sweaty Koul, Hari K Koul
Department of Biochemistry and Molecular Biology, LSU Health Sciences Center, Shreveport, Louisiana., Feist Weiller Cancer Center, Shreveport, Louisiana.