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

Ji, Ke, Ye, Lin ORCID: https://orcid.org/0000-0002-0303-2409, Ruge, Fiona, Hargest, Rachel ORCID: https://orcid.org/0000-0001-9830-3832, Mason, Malcolm David ORCID: https://orcid.org/0000-0003-1505-2869 and Jiang, Wen Guo ORCID: https://orcid.org/0000-0002-3283-1111 2014. Implication of metastasis suppressor gene, Kiss-1 and its receptor Kiss-1R in colorectal cancer. BMC Cancer 14 , 723. 10.1186/1471-2407-14-723

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Additional Information:	This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Publisher:	BioMed Central
ISSN:	1471-2407
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	19 September 2014
Last Modified:	09 May 2023 19:32
URI:	https://orca.cardiff.ac.uk/id/eprint/75780

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