Gauri Shishodia1,2, Sweaty Koul2,3, Hari K Koul1,2,4. 1. Department of Biochemistry and Molecular Biology, LSU Health Sciences Center, Shreveport, Louisiana. 2. Feist Weiller Cancer Center, Shreveport, Louisiana. 3. Department of Urology, LSU Health Sciences Center, Shreveport, Louisiana. 4. Overton Brooks Veterans Administrative Medical Center, Shreveport, Louisiana.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: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. RESULTS: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 TRAMPmice. 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. CONCLUSIONS: 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.
Authors: Chenxi Wang; Ang Chen; Banzhan Ruan; Zubiao Niu; Yan Su; Hongquan Qin; You Zheng; Bo Zhang; Lihua Gao; Zhaolie Chen; Hongyan Huang; Xiaoning Wang; Qiang Sun Journal: Front Cell Dev Biol Date: 2020-05-08
Authors: Xiajie Zhang; Kira Groen; Brianna C Morten; Luiza Steffens Reinhardt; Hamish G Campbell; Antony W Braithwaite; Jean-Christophe Bourdon; Kelly A Avery-Kiejda Journal: Mol Oncol Date: 2021-11-23 Impact factor: 6.603