Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

Implication of metastasis suppressor gene, Kiss-1 and its receptor Kiss-1R in colorectal cancer

Authors: Ke Ji, Lin Ye, Fiona Ruge, Rachel Hargest, Malcolm D Mason, Wen G Jiang

Published in: BMC Cancer | Issue 1/2014

Login to get access

Abstract

Background

Kiss-1 and Kiss-1R have been suggested as a novel pair of metastasis suppressors for several human solid tumours, however, their role in colorectal cancer remains largely unknown. Therefore, the aim of this study was to investigate the role and signal transduction of Kiss-1 and Kiss-1R in colorectal cancer.

Methods

Ribozyme transgenes were used to knockdown high expression of Kiss-1 and Kiss-1R in HT115 and HRT18 cells. The stabilized transfected cells were then used to deduce the influence of Kiss-1 and Kiss-1R on the function of colorectal cancer cells by in vitro assays and ECIS assay. The effect of Kiss-1 on MMPs related to tumour metastasis was also deleted by zymography. The mRNA and protein expression of Kiss-1 and Kiss-1R, and their correlation to the clinical outcome in human colorectal cancer were investigated using real-time PCR and IHC respectively.

Results

Knocking down Kiss-1 resulted in increased invasion and migration of colorectal cancer cells. Kisspeptin-10 decreased cellular migration of colorectal cancer cells and required ERK signaling as shown during the ECIS based analyses. Reduction of MMP-9 was caused by Kisspeptin-10 and ERK inhibitor, shown by zymography. In human colorectal cancer tissues, the mRNA expression level of Kiss-1 had a negative correlation with Dukes staging, TNM staging, tumour size and lymph node involvement. Reduction of Kiss-1R was also linked to poor prognosis for the patients.

Conclusions

The present study has presented evidence that Kiss-1 may be a putative metastasis suppressor molecule in human colorectal cancer.
Appendix
Available only for authorised users
Literature
1.
Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 2005, 55 (2): 74-108. 10.3322/canjclin.55.2.74.CrossRefPubMed
2.
Welch DR, Chen P, Miele ME, McGary CT, Bower JM, Stanbridge EJ, Weissman BE: Microcell-mediated transfer of chromosome 6 into metastatic human C8161 melanoma cells suppresses metastasis but does not inhibit tumorigenicity. Oncogene. 1994, 9 (1): 255-262.PubMed
3.
Bilban M, Ghaffari-Tabrizi N, Hintermann E, Bauer S, Molzer S, Zoratti C, Malli R, Sharabi A, Hiden U, Graier W, Knofler M, Andreae F, Wagner O, Quaranta V, Desoye G: Kisspeptin-10, a KiSS-1/metastin-derived decapeptide, is a physiological invasion inhibitor of primary human trophoblasts. J Cell Sci. 2004, 117 (Pt 8): 1319-1328.CrossRefPubMed
4.
Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden JM, Le Poul E, Brezillon S, Tyldesley R, Suarez-Huerta N, Vandeput F, Blanpain C, Schiffmann SN, Vassart G, Parmentier M: The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem. 2001, 276 (37): 34631-34636. 10.1074/jbc.M104847200.CrossRefPubMed
5.
Ohtaki T, Shintani Y, Honda S, Matsumoto H, Hori A, Kanehashi K, Terao Y, Kumano S, Takatsu Y, Masuda Y, Ishibashi Y, Watanabe T, Asada M, Yamada T, Suenaga M, Kitada C, Usuki S, Kurokawa T, Onda H, Nishimura O, Fujino M: Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature. 2001, 411 (6837): 613-617. 10.1038/35079135.CrossRefPubMed
6.
Lee DK, Nguyen T, O’Neill GP, Cheng R, Liu Y, Howard AD, Coulombe N, Tan CP, Tang-Nguyen AT, George SR, O’Dowd BF: Discovery of a receptor related to the galanin receptors. FEBS Lett. 1999, 446 (1): 103-107. 10.1016/S0014-5793(99)00009-5.CrossRefPubMed
7.
Sanchez-Carbayo M, Capodieci P, Cordon-Cardo C: Tumor suppressor role of KiSS-1 in bladder cancer: loss of KiSS-1 expression is associated with bladder cancer progression and clinical outcome. Am J Pathol. 2003, 162 (2): 609-617. 10.1016/S0002-9440(10)63854-0.CrossRefPubMedPubMedCentral
8.
Wang H, Jones J, Turner T, He QP, Hardy S, Grizzle WE, Welch DR, Yates C: Clinical and biological significance of KISS1 expression in prostate cancer. Am J Pathol. 2012, 180 (3): 1170-1178. 10.1016/j.ajpath.2011.11.020.CrossRefPubMedPubMedCentral
9.
Dhar DK, Naora H, Kubota H, Maruyama R, Yoshimura H, Tonomoto Y, Tachibana M, Ono T, Otani H, Nagasue N: Downregulation of KiSS-1 expression is responsible for tumor invasion and worse prognosis in gastric carcinoma. Int J Cancer. 2004, 111 (6): 868-872. 10.1002/ijc.20357.CrossRefPubMed
10.
Ikeguchi M, Yamaguchi K, Kaibara N: Clinical significance of the loss of KiSS-1 and orphan G-protein-coupled receptor (hOT7T175) gene expression in esophageal squamous cell carcinoma. Clin Cancer Res. 2004, 10 (4): 1379-1383. 10.1158/1078-0432.CCR-1519-02.CrossRefPubMed
11.
Masui T, Doi R, Mori T, Toyoda E, Koizumi M, Kami K, Ito D, Peiper SC, Broach JR, Oishi S, Niida A, Fujii N, Imamura M: Metastin and its variant forms suppress migration of pancreatic cancer cells. Biochem Biophys Res Commun. 2004, 315 (1): 85-92. 10.1016/j.bbrc.2004.01.021.CrossRefPubMed
12.
Nomura H, Sato H, Seiki M, Mai M, Okada Y: Expression of membrane-type matrix metalloproteinase in human gastric carcinomas. Cancer Res. 1995, 55 (15): 3263-3266.PubMed
13.
Olbrich T, Ziegler E, Turk G, Schubert A, Emons G, Grundker C: Kisspeptin-10 inhibits bone-directed migration of GPR54-positive breast cancer cells: evidence for a dose-window effect. Gynecol Oncol. 2010, 119 (3): 571-578. 10.1016/j.ygyno.2010.08.018.CrossRefPubMed
14.
15.
Jiang WG, Martin TA, Lewis-Russell JM, Douglas-Jones A, Ye L, Mansel RE: Eplin-alpha expression in human breast cancer, the impact on cellular migration and clinical outcome. Mol Cancer. 2008, 7: 71-CrossRefPubMedPubMedCentral
16.
Sun PH, Ye L, Mason MD, Jiang WG: Protein tyrosine phosphatase micro (PTP micro or PTPRM), a negative regulator of proliferation and invasion of breast cancer cells, is associated with disease prognosis. PLoS One. 2012, 7 (11): e50183-10.1371/journal.pone.0050183.CrossRefPubMedPubMedCentral
17.
Navenot JM, Wang Z, Chopin M, Fujii N, Peiper SC: Kisspeptin-10-induced signaling of GPR54 negatively regulates chemotactic responses mediated by CXCR4: a potential mechanism for the metastasis suppressor activity of kisspeptins. Cancer Res. 2005, 65 (22): 10450-10456. 10.1158/0008-5472.CAN-05-1757.CrossRefPubMed
18.
Moya P, Esteban S, Fernandez-Suarez A, Maestro M, Morente M, Sánchez-Carbayo M: KiSS-1 methylation and protein expression patterns contribute to diagnostic and prognostic assessments in tissue specimens for colorectal cancer. Tumour Biol. 2013, 34 (1): 471-479. 10.1007/s13277-012-0572-3.CrossRefPubMed
19.
Ringel MD, Hardy E, Bernet VJ, Burch HB, Schuppert F, Burman KD, Saji M: Metastin receptor is overexpressed in papillary thyroid cancer and activates MAP kinase in thyroid cancer cells. J Clin Endocrinol Metab. 2002, 87 (5): 2399-10.1210/jcem.87.5.8626.CrossRefPubMed
20.
Yoshioka K, Ohno Y, Horiguchi Y, Ozu C, Namiki K, Tachibana M: Effects of a KiSS-1 peptide, a metastasis suppressor gene, on the invasive ability of renal cell carcinoma cells through a modulation of a matrix metalloproteinase 2 expression. Life Sci. 2008, 83 (9–10): 332-338.CrossRefPubMed
21.
Yan C, Wang H, Boyd DD: KiSS-1 represses 92-kDa type IV collagenase expression by down-regulating NF-kappa B binding to the promoter as a consequence of Ikappa Balpha -induced block of p65/p50 nuclear translocation. J Biol Chem. 2001, 276 (2): 1164-1172. 10.1074/jbc.M008681200.CrossRefPubMed
22.
Ziegler E, Olbrich T, Emons G, Grundker C: Antiproliferative effects of kisspeptin10 depend on artificial GPR54 (KISS1R) expression levels. Oncol Rep. 2013, 29 (2): 549-554.PubMed
Metadata
Title
Implication of metastasis suppressor gene, Kiss-1 and its receptor Kiss-1R in colorectal cancer
Authors
Ke Ji
Lin Ye
Fiona Ruge
Rachel Hargest
Malcolm D Mason
Wen G Jiang
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-723

Other articles of this Issue 1/2014

BMC Cancer 1/2014 Go to the issue

Research article

Clinical implications of SPRR1A expression in diffuse large B-cell lymphomas: a prospective, observational study

Research article

Clinical relevance of breast cancer-related genes as potential biomarkers for oral squamous cell carcinoma

Research article

Epstein-Barr virus infection and clinical outcome in breast cancer patients correlate with immune cell TNF-α/IFN-γ response

Research article

Special role of Foxp3 for the specifically altered microRNAs in Regulatory T cells of HCC patients

Research article

An epidemiological study assessing the prevalence of human papillomavirus types in women in the Kingdom of Bahrain

Research article

MicroRNA-1269 promotes proliferation in human hepatocellular carcinoma via downregulation of FOXO1
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits