Tumor promotion or suppression: Revisiting the role of EXT1 and Heparan sulfate.

IF 2 4区 生物学 Q3 CELL BIOLOGY
Ayumi Niwa, Hiroyuki Tomita, Akira Hara
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引用次数: 0

Abstract

Heparan sulfate (HS), a linear sulfated polysaccharide attached to proteoglycans, modulates the availability and activity of growth factors and cytokines to regulate cell signaling, adhesion, and migration. Exostosin-1 (EXT1), a key glycosyltransferase for HS chain elongation, is increasingly implicated in cancer development and progression. Although originally identified as a tumor suppressor in hereditary multiple exostoses, EXT1 exhibits a complex, context-dependent role in cancer. The effects of EXT1 in cancer differ by cell and tumor type, exerting both tumor-suppressing and tumor-promoting effects. Notably, EXT1 also alters the tumor microenvironment via its expression in stromal fibroblasts and endothelial cells, further influencing tumor behavior. This review discusses the functions of HS and EXT1, emphasizing the roles of EXT1 in cancer and its microenvironment. A deeper understanding of these mechanisms may offer novel therapies targeting the HS biosynthetic pathway.

肿瘤促进或抑制:重新审视EXT1和硫酸肝素的作用。
硫酸乙酰肝素(HS)是一种附着在蛋白聚糖上的线性硫酸化多糖,可调节生长因子和细胞因子的可用性和活性,从而调节细胞信号传导、粘附和迁移。Exostosin-1 (EXT1)是HS链延伸的关键糖基转移酶,在癌症的发生和进展中越来越重要。虽然最初被认为是遗传性多发性外生瘤的肿瘤抑制因子,但EXT1在癌症中表现出复杂的、依赖于环境的作用。EXT1在肿瘤中的作用因细胞和肿瘤类型的不同而不同,具有抑制肿瘤和促进肿瘤的作用。值得注意的是,EXT1还通过其在间质成纤维细胞和内皮细胞中的表达改变肿瘤微环境,进一步影响肿瘤行为。本文综述了HS和EXT1的功能,重点介绍了EXT1在肿瘤及其微环境中的作用。对这些机制的深入了解可能会提供针对HS生物合成途径的新疗法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Histology and histopathology
Histology and histopathology 生物-病理学
CiteScore
3.90
自引率
0.00%
发文量
232
审稿时长
2 months
期刊介绍: HISTOLOGY AND HISTOPATHOLOGY is a peer-reviewed international journal, the purpose of which is to publish original and review articles in all fields of the microscopical morphology, cell biology and tissue engineering; high quality is the overall consideration. Its format is the standard international size of 21 x 27.7 cm. One volume is published every year (more than 1,300 pages, approximately 90 original works and 40 reviews). Each volume consists of 12 numbers published monthly online. The printed version of the journal includes 4 books every year; each of them compiles 3 numbers previously published online.
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