The Hematopoietic Stem Cell Regulatory Gene Latexin Has Tumor-suppressive Properties in Malignant Melanoma

Overview

Journal J Invest Dermatol

Publisher Elsevier

Specialty Dermatology

Date 2013 Feb 1

PMID 23364479

Citations 20

Authors

Viswanathan Muthusamy

Sanjay Premi

Cara Soper

James Platt

Marcus Bosenberg

Affiliations

Soon will be listed here.

Abstract

Despite recent advancements in therapy, melanoma remains a highly lethal skin cancer. A better understanding of the genetic and epigenetic changes responsible for melanoma formation and progression could result in the development of more effective treatments. Advanced melanomas are known to exhibit widespread promoter region CpG island methylation leading to the inactivation of key tumor suppressor genes. Meta-analyses of relevant microarray data sets revealed the hematopoietic stem cell regulator gene latexin (LXN) to be commonly downregulated in approximately 50% of melanomas. The CpG island in the promoter region of LXN was almost universally hypermethylated in melanoma cell lines and tumors, and treatment of the cell lines with the demethylating drug 5-aza-2'-deoxycytidine resulted in increased LXN expression. In this paper, we demonstrate that the exogenous expression of LXN in melanoma cell lines results in a significant inhibition of tumor cell proliferation. In addition, we show that the increased expression of LXN in these lines correlates with reduction in the expression levels of stem cell transcription factors OCT4, NANOG, SOX2, KLF4, and MYCN, indicating that LXN may exert its tumor-suppressive function by altering the stem cell-like properties of melanoma cells.

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Latexin regulation by HMGB2 is required for hematopoietic stem cell maintenance.

Zhang C, Fondufe-Mittendorf Y, Wang C, Chen J, Cheng Q, Zhou D Haematologica. 2019; 105(3):573-584.

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The putative tumour suppressor protein Latexin is secreted by prostate luminal cells and is downregulated in malignancy.

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Epigenetic markers in melanoma.

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