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PACAP inhibits tumor growth and interferes with clusterin in cervical carcinomas
Author(s) -
Lee Ji-Hae,
Lee Ji-Yeon,
Rho Seung Bae,
Choi Jong-Soon,
Lee Dong-Gi,
An Sungwhan,
Oh Taejeong,
Choi Don-Chan,
Lee Seung-Hoon
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.11.004
Subject(s) - clusterin , cancer research , cervical carcinoma , medicine , chemistry , apoptosis , cervical cancer , cancer , biochemistry
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.