The KISS1 metastasis suppressor: mechanistic insights and clinical utility

Kevin, T. Nash

doi:10.2741/1824

Cited by 77 publications

(85 citation statements)

References 57 publications

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“…Careful examination of the sequence revealed that KISS1 has characteristics in common with neuropeptides, which include a secretion signal, several dibasic cleavage sites and a cleavage amidation site. 19 Structures derived from the neuronal system, such as the optic nerve and retina, may present cross reactivity.…”

Section: Discussionmentioning

confidence: 99%

“…19 Experimental evidence to date suggests that KISS1 may suppress metastatic proliferation at the secondary site in several ways. One of the mechanisms suggests that secreted kisspeptins, or stromal peptides induced by kisspeptins, may deposit in the extracellular matrix altering its organization, structure, or composition in such a way that it provides an antiproliferative signal to adjacent metastatic cells.…”

Section: Discussionmentioning

confidence: 99%

“…One of the mechanisms suggests that secreted kisspeptins, or stromal peptides induced by kisspeptins, may deposit in the extracellular matrix altering its organization, structure, or composition in such a way that it provides an antiproliferative signal to adjacent metastatic cells. 19 This mechanism may, in part, be explained by the way KISS1 interacts with metalloproteinases (MMPs).…”

Section: Discussionmentioning

confidence: 99%

“…16 In general, loss or reduction of KISS1 expression in several different tumour types negatively affects survival. 19 KISS1 encodes a 145 amino-acid residue peptide that is further processed. One of the products, a 54 amino-acid peptide, is called Metastin or Kisspeptin-54 and is a natural ligand to a G-coupled receptor known as GPR54.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, a better understanding of these processes is essential to develop novel and specific drugs to prevent and treat UM metastasis. However, to date, characterization of KISS1 expression in melanoma has only been undertaken in skin melanoma 19 and remains to be investigated in UM.…”

Section: Introductionmentioning

confidence: 99%

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Expression of the metastasis suppressor gene KISS1 in uveal melanoma

Martins

Fernandes

Antecka

et al. 2008

Eye

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Purpose Uveal melanoma (UM) is the most common primary malignant intraocular tumour in adults. Forty-five percent of UM patients develop metastasis within 15 years of initial diagnosis. KISS1, a human metastasis suppressor gene, has been reported to play a role in various human malignancies. The purpose of this study was to investigate the expression of KISS1 in UM and its potential value as a prognostic marker. Methods Thirty-seven cases of paraffinembedded human UM specimens were immunostained with a KISS1 antibody. Clinical-pathological data were obtained. The relationship between the clinical-pathological data and the expression of KISS1 was evaluated. Moreover, the survival rates of the patients were also assessed. Five UM cell lines (92.1, OCM-1, MKTBR, UW1 and SP6.5) were assayed for KISS1 expression. In addition, real-time PCR was used to determine mRNA levels of KISS1 and its receptor GPR54 in these cell lines. Results The immunohistochemical results of KISS1 expression displayed cytoplasmic staining in 84% of UM specimens. Low KISS1 expression was associated with a higher risk of metastatic disease (Po0.05). Furthermore, we found that KISS1 was expressed in all five UM cells lines. Real-time PCR analysis confirmed the presence of both KISS1 and its receptor GPR54 in all five human UM cell lines. Conclusions To the best of our knowledge, this is the first time that KISS1 has been characterized in UM. The correlation between KISS1 expression and UM survival rate suggests an important role for KISS1 as a prognostic marker in this particular tumour.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Expression of the metastasis suppressor gene KISS1 in uveal melanoma

Martins

Fernandes

Antecka

et al. 2008

Eye

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N‐myc downstream regulated gene 1 modulates Wnt‐β‐catenin signalling and pleiotropically suppresses metastasis

et al. 2012

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Wnt signalling has pivotal roles in tumour progression and metastasis; however, the exact molecular mechanism of Wnt signalling in the metastatic process is as yet poorly defined. Here we demonstrate that the tumour metastasis suppressor gene, NDRG1, interacts with the Wnt receptor, LRP6, followed by blocking of the Wnt signalling, and therefore, orchestrates a cellular network that impairs the metastatic progression of tumour cells. Importantly, restoring NDRG1 expression by a small molecule compound significantly suppressed the capability of otherwise highly metastatic tumour cells to thrive in circulation and distant organs in animal models. In addition, our analysis of clinical cohorts data indicate that Wnt+/NDRG−/LRP+ signature has a strong predictable value for recurrence-free survival of cancer patients. Collectively, we have identified NDRG1 as a novel negative master regulator of Wnt signalling during the metastatic progression, which opens an opportunity to define a potential therapeutic target for metastatic disease.

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Locked Dimerized CXCL12 Exerts Radiosensitizing Effects in Head and Neck Cancer

Espinosa,

Awan,

Memon

et al. 2024

Head & Neck

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BackgroundHead and neck squamous cell carcinoma (HNSCC) presents significant treatment challenges, particularly in cases unrelated to human papillomavirus (HPV). The chemokine receptor CXCR4, interacting with its ligand CXCL12, plays a crucial role in tumor proliferation, metastasis, and treatment resistance. This study explores the therapeutic potential of engineered monomeric and dimerized CXCL12 variants (CXCL121 and CXCL122, respectively) in HNSCC and evaluates potential additive effects when combined with radiation therapy.MethodsClinical HNSCC biopsies were evaluated for CXCR4 expression in both previously untreated and radiorecurrent disease. HNSCC cell lines were then treated with combinations of CXCL12 variants and radiotherapy and interrogated for proliferation, gene expression change, and underlying molecular mechanisms. In vivo studies evaluated the biodistribution of engineered CXCL12 and tested these treatments in humanized cell line‐derived xenograft (CDX) models.ResultsCXCL122 significantly reduced HNSCC cell proliferation and enhanced the effects of radiotherapy, likely through biased agonism at the CXCR4 receptor and upregulation of the KISS1R pathway. In vivo, CXCL122 localized to tumor sites and augmented the effects of radiation to inhibit tumor growth.ConclusionsCXCL122, in combination with radiation, demonstrates potent anti‐tumor effects in HNSCC. These findings support further clinical investigation of CXCL122 to enhance the effects of radiotherapy.

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The KISS1 metastasis suppressor: mechanistic insights and clinical utility

Cited by 77 publications

References 57 publications

Expression of the metastasis suppressor gene KISS1 in uveal melanoma

Expression of the metastasis suppressor gene KISS1 in uveal melanoma

N‐myc downstream regulated gene 1 modulates Wnt‐β‐catenin signalling and pleiotropically suppresses metastasis

Locked Dimerized CXCL12 Exerts Radiosensitizing Effects in Head and Neck Cancer

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