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

BMC Cancer

Ke Ji²  Lin Ye²  Fiona Ruge²  Rachel Hargest²  Malcolm D Mason¹  Wen G Jiang² 

[1] Section of Oncology & Palliative Medicine, Cardiff University School of Medicine Velindre Hospital, Cardiff CF14 2TL, UK

[2] Cardiff University-Peking University Joint Oncology Institute, Metastasis & Angiogenesis Research Group, Cardiff University School of Medicine, Cardiff CF14 4XN, UK

关键词: ERK signal pathway;    MMP-9;    Invasion;    Migration;    Colorectal cancer;    GPR54;    Kiss-1R;    Kiss-1;    Metastasis suppressor gene;   

Others  :  1121017
DOI  :  10.1186/1471-2407-14-723

 received in 2014-06-02, accepted in 2014-09-19,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Ji et al.; licensee BioMed Central Ltd.

【 图 表 】

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