PACAP inhibits tumor growth and interferes with clusterin in cervical carcinomas.
Secretory clusterin (sCLU), an anti-apoptotic protein, is overexpressed in many tumors and enhances tumorigenesis and chemo-resistance. However, the regulation mechanism controlling the sCLU maturation process or activity remains undetermined. In this study, we found PACAP as a negative regulator of CLU. Overexpression of the PACAP gene in cervical cancer cell ... lines lacking PACAP expression significantly inhibited cell growth and induced apoptosis. We further demonstrated that interaction of PACAP with CLU significantly downregulated CLU expression and secretion, inhibited the Akt-Raf-ERK pathway, and suppressed the growth of human tumor xenografts in nude mice. This novel inhibitory function of PACAP may be applicable for developing novel molecular therapies for tumors with increased sCLU expression.
Mesh Terms:
Animals, Apoptosis, Cell Line, Tumor, Cell Proliferation, Cell Survival, Cell Transformation, Neoplastic, Clusterin, Extracellular Signal-Regulated MAP Kinases, Female, Humans, Mice, Pituitary Adenylate Cyclase-Activating Polypeptide, Protein Structure, Tertiary, Protein Transport, Proto-Oncogene Proteins c-akt, Signal Transduction, Uterine Cervical Neoplasms, raf Kinases
Animals, Apoptosis, Cell Line, Tumor, Cell Proliferation, Cell Survival, Cell Transformation, Neoplastic, Clusterin, Extracellular Signal-Regulated MAP Kinases, Female, Humans, Mice, Pituitary Adenylate Cyclase-Activating Polypeptide, Protein Structure, Tertiary, Protein Transport, Proto-Oncogene Proteins c-akt, Signal Transduction, Uterine Cervical Neoplasms, raf Kinases
FEBS Lett.
Date: Dec. 20, 2014
PubMed ID: 25451228
View in: Pubmed Google Scholar
Download Curated Data For This Publication
187297
Switch View:
- Interactions 2