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PMID: 16283480 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

KiSS1 suppresses metastasis in human ovarian cancer via inhibition of protein kinase C alpha.

Clinical & experimental metastasis ·Vol. 22 ·No. 5 ·2005-00-00 ·Pages 369-76

Jiang Y, Berk M, Singh LS, Tan H, Yin L, Powell CT, Xu Y

Abstract

Metastasis is a vital target for cancer treatment, since the majority of cancer patients die from metastatic, rather than the primary disease. KiSS1 has been identified as a metastasis suppressor gene in melanoma and breast carcinomas. We show here that KiSS1 is also a metastasis suppressor in human ovarian cancer. Overexpression of KiSS1 in ovarian cancer cells inhibits cell migration induced by serum or lysophosphatidic acid (LPA), and colonization in soft agar, but not cell proliferation, representing the characteristics of a metastasis suppressor gene. Furthermore, using an experimental metastatic mouse model, we show that expression of KiSS1 in SKOV3 ovarian cancer cells suppresses >50% metastatic colonization in mice (P < 0.0001). We find that activating protein kinase C (PKC) reverses about 80% of the inhibited cell migration induced by KiSS1, while down-regulation of PKCalpha with shRNA restores KiSS1 effect, providing evidence that inhibiting PKCalpha may be an important mechanism of the effect of KiSS1. These results suggest that KiSS1 is a metastasis suppressor of ovarian cancer and may be a potential molecular target for the treatment.

MeSH Terms
Animals Cell Movement/physiology Cell Proliferation Down-Regulation Female Humans Kisspeptins Lysophospholipids/physiology Mice Mice, Nude Neoplasm Metastasis/physiopathology Ovarian Neoplasms/genetics,physiopathology Protein Kinase C-alpha/antagonists & inhibitors,physiology Proteins/physiology Transplantation, Heterologous Tumor Suppressor Proteins
Chemicals
KISS1 protein, human Kisspeptins Lysophospholipids Proteins Tumor Suppressor Proteins Protein Kinase C-alpha lysophosphatidic acid
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Jiang Ying
Department of Cancer Biology, The Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Berk Michael
Singh Lisam Shanjukumar
Tan Haiyan
Yin Lihong
Powell C Thomas
Xu Yan
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Article Info
Journal
Clinical & experimental metastasis
Abbr.
Clin Exp Metastasis
ISSN
0262-0898
DOI
10.1007/s10585-005-8186-4
Published
2005-00-00
Pages
369-76
Language
English
Region
Netherlands
NLM ID
8409970
Subset
IM
Grants
NCI NIH HHS · CA-89228 · United States
NCI NIH HHS · R01 CA095042 · United States
External Links
PubMed source DOI: 10.1007/s10585-005-8186-4 View journal details
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