Journal
FEBS LETTERS
Volume 588, Issue 24, Pages 4730-4739Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2014.11.004
Keywords
Clusterin; Pituitary adenylate cyclase-activating polypeptide; Cervical cancer; Apoptosis; Akt/Raf/ERK pathway
Funding
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2014R1A1A2055411]
- Korea Basic Science Institute [D34403]
- Yongin University fund
- National Research Foundation of Korea [2014R1A1A2055411] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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