KiSS-1, a Novel Human Malignant Melanoma Metastasis-Suppressor Gene

Lee, Jeong Hyung; Miele, Monica; Hicks, Deana J.; Phillips, Karen K.; Trent, Jeffery M.; Weissman, Bernard E.; Welch, Danny R.

doi:10.1093/jnci/88.23.1731

Cited by 916 publications

(738 citation statements)

References 36 publications

(32 reference statements)

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“…The gene from which kisspeptins are transcribed, KISS1, is a tumor-suppressor gene in breast cancer cells, but later work has also identified products of this gene as an energy sensor (Lee et al, 1996). Earlier studies showed that GPR54 is expressed in hypothalamic neurons as well as in the pancreas and the placenta (Kotani et al, 2001).…”

Section: Gpr54mentioning

confidence: 99%

G-protein-coupled receptors and islet function—Implications for treatment of type 2 diabetes

Winzell

Åhrén

2007

Pharmacology & Therapeutics

161

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Islet function is regulated by a number of different signals. A main signal is generated by glucose, which stimulates insulin secretion and inhibits glucagon secretion. The glucose effects are modulated by many factors, including hormones, neurotransmitters and nutrients. Several of these factors signal through guanine nucleotide-binding protein (G-protein) coupled receptors (GPCRs). Examples of islet GPCRs are GPR40 and GPR119, which are GPCRs with fatty acids as ligands, the receptors for the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), the receptors for the islet hormones glucagon and somatostatin, the receptors for the classical neurotransmittors

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Section: Gpr54mentioning

confidence: 99%

G-protein-coupled receptors and islet function—Implications for treatment of type 2 diabetes

Winzell

Åhrén

2007

Pharmacology & Therapeutics

161

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“…1 To date, only a few such molecules are discovered and among them KiSS-1 is only recently discovered as a promising metastasis suppressor gene. 2 The KiSS-1 cDNA was originally cloned by subtraction hybridization between a metastatic and a nonmetastatic melanoma cell line and has been proved to be competent in ameliorating the metastatic potentiality of several cancer cell lines in in vitro study. 2,3 Significant reduction in KiSS-1 or metastin expression in tumors with high metastatic potential has been reported.…”

mentioning

confidence: 99%

“…2 The KiSS-1 cDNA was originally cloned by subtraction hybridization between a metastatic and a nonmetastatic melanoma cell line and has been proved to be competent in ameliorating the metastatic potentiality of several cancer cell lines in in vitro study. 2,3 Significant reduction in KiSS-1 or metastin expression in tumors with high metastatic potential has been reported. 4 -6 Moreover, reduced KiSS-1 expression became a strong prognostic marker in patients with urinary bladder cancer.…”

mentioning

confidence: 99%

Downregulation of KiSS‐1 expression is responsible for tumor invasion and worse prognosis in gastric carcinoma

Dhar

Naora

Kubota

et al. 2004

Intl Journal of Cancer

119

104

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KiSS-1 is a promising candidate tumor-suppressor gene and may play a key role in the metastatic cascade. The expression profile and the role of KiSS-1 in cancer progression are largely unknown in most of the cancers, including gastric cancer. In this study, KiSS-1 expression was evaluated by RNase protection assay and localization was done by in situ hybridization in 40 gastric cancers and their adjacent normal gastric mucosa. For comparison with clinicopathologic characteristics and patient prognosis, all patients were divided into 2 groups having high and low KiSS-1 expression by using the median as the cutoff value of KiSS-1 expression as determined by the RNase protection assay. Gastric cancers with low KiSS-1 had frequent venous invasion, distant metastasis and tumor recurrence. Accordingly, patients with low KiSS-1-expressing tumors had a significantly worse overall and disease-free survival. In multivariate analysis, KiSS-1 became the strongest independent prognostic factor among the conventional prognosticators for gastric cancer patients. Collectively, these findings suggest that KiSS-1 may play a crucial role in gastric cancer invasion and could be a useful target for therapeutic intervention.

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“…1,2 Metastatic phenotypes have been linked to such genes as NME1 (17q), CDH1 (16q), BRMS1 (11q) and KISS1 (1q). 1,[3][4][5] LOH analyses have defined regions of deletion associated with metastasis on chromosomes 3p21, 15q14, 16q22 and 11p15. 2,6 Frequent genetic alterations on chromosome 11p15 suggest a crucial role for this region in breast 6,7 and other adult 8 -12 and childhood cancers.…”

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confidence: 99%

Suppression of malignant growth of human breast cancer cells by ectopic expression of integrin‐linked kinase

Chen

Shen

Karnik

2004

Intl Journal of Cancer

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Allelic loss at the short arm of chromosome 11 is one of the most common and potent events in the progression and metastasis of breast cancer. Here, we present evidence that the Integrin-Linked Kinase (ILK) gene maps to the commonly deleted chromosome 11p15. Genetic alterations that occur in breast cancer are believed to be of importance for initiation as well as progression of the disease. These genetic alterations lead to the loss or activation of a number of critical genes, such as those involved in cell proliferation, differentiation, apoptosis and genetic stability. The genetic abnormalities most frequently observed in breast tumors are amplification of proto-oncogenes (MYC, ERBB2 and CCND1), mutations of TP53 and loss of heterozygosity (LOH) on chromosomes 3p, 6q, 7q, 8p, 9p, 11, 13q, 17, 18q and 22q. 1,2 Metastatic phenotypes have been linked to such genes as NME1 (17q), CDH1 (16q), BRMS1 (11q) and KISS1 (1q). 1,3-5 LOH analyses have defined regions of deletion associated with metastasis on chromosomes 3p21, 15q14, 16q22 and 11p15. 2,6 Frequent genetic alterations on chromosome 11p15 suggest a crucial role for this region in breast 6,7 and other adult 8 -12 and childhood cancers. [13][14][15][16][17] More recently, we have mapped 2 distinct regions on chromosome 11p15.5 that are subject to LOH during breast tumor progression and metastasis. 6 LOH at region 1 correlated with tumors that contain ductal carcinoma in situ, suggesting that the loss of a critical gene in this region may be responsible for early events in malignancy. LOH at region 2 correlated with a more aggressive tumor and an ominous outlook for the patient, such as aneuploidy, high S-phase fraction and the presence of metastasis in regional lymph nodes. Although considerable advances have been made in the fine-mapping of chromosome 11p15.5, the tumor/metastasis suppressor gene(s) encoded by this region has evaded identification.Integrin-linked kinase (ILK) is an intriguing serine/threonine kinase that has been implicated in integrin-, growth-factor-and Wnt-signaling pathways. 18 It binds to the cytoplasmic domains of ␤1 and ␤3 integrins and mediates the downstream signaling events in integrin function. 19 Interactions between integrins and their ligands are involved in the regulation of many cellular functions, including embryonic development, cell proliferation, tumor growth and the ability to metastasize. 20 In Drosophila, the absence of ILK function causes defects similar to loss of integrin adhesion, and ILK mutations cause embryonic lethality and defects in muscle attachment. 21 Although ILK maps to the commonly deleted chromosome 11p, the potential of this gene in tumor/metastasis suppression has not been evaluated. We have therefore analyzed the effect of ILK expression on the in vitro and in vivo tumor growth and invasion of human mammary carcinoma cells. MATERIAL AND METHODS Mapping of ILK to LOH region 2Two YAC clones (847a12 and 696H10), a BAC clone (BAC 1760) and a PAC clone (PAC1331) overlapped the LOH region 2 and were used to...

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KiSS-1, a Novel Human Malignant Melanoma Metastasis-Suppressor Gene

Abstract: KiSS-1 may be a useful marker for distinguishing metastatic melanomas from nonmetastatic melanomas.

Cited by 916 publications

References 36 publications

G-protein-coupled receptors and islet function—Implications for treatment of type 2 diabetes

G-protein-coupled receptors and islet function—Implications for treatment of type 2 diabetes

Downregulation of KiSS‐1 expression is responsible for tumor invasion and worse prognosis in gastric carcinoma

Suppression of malignant growth of human breast cancer cells by ectopic expression of integrin‐linked kinase

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