Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB) and Cancer: A Novel Potential Therapeutic Target.
Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB) and Cancer: A Novel Potential Therapeutic Target.
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DOI：
10.1016/j.steroids.2017.10.013
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发表时间：
2018-05
期刊：
影响因子：
2.7
通讯作者：
Hammes SR
中科院分区：
文献类型：
--
作者：
Taya M;Hammes SR
糖蛋白非转移性黑素瘤蛋白B（GPNMB）是在癌细胞（包括黑素瘤、胶质母细胞瘤和三阴性乳腺癌）的细胞表面上富集的跨膜蛋白。越来越多的证据表明GPNMB是一种肿瘤促进剂;然而，尽管其具有生物学和临床意义，但GPNMB促进肿瘤发生的分子机制尚未得到很好的理解。GPNMB促进侵袭性行为，如肿瘤细胞增殖、迁移和侵袭。从细胞表面脱落的GPNMB的胞外结构域与整联蛋白相互作用，以促进免疫抑制性和促血管生成细胞向肿瘤微环境的募集，从而增强肿瘤迁移和侵袭。GPNMB还以细胞自主方式调节受体酪氨酸激酶和整联蛋白信号传导，导致下游激酶信号传导，所述下游激酶信号传导继而触发致瘤因子如基质金属蛋白酶（MMP）和细胞因子的表达和分泌。因此，GPNMB通过脱落其细胞外结构域在细胞内和以旁分泌方式发挥其促肿瘤发生作用。这篇综述强调了GPNMB在肿瘤进展中的重要性，并讨论了GPNMB诱导的肿瘤生长和侵袭的分子介质。
Glycoprotein non-metastatic melanoma protein B (GPNMB) is a transmembrane protein enriched on the cell surface of cancer cells, including melanoma, glioblastoma, and triple-negative breast cancer. There is growing evidence identifying GPNMB as a tumor-promoter; however, despite its biological and clinical significance, the molecular mechanisms engaged by GPNMB to promote tumorigenesis are not well understood. GPNMB promotes aggressive behaviors such as tumor cell proliferation, migration, and invasion. The extracellular domain of GPNMB shed from the cell surface interacts with integrins to facilitate in the recruitment of immune-suppressive and pro-angiogenic cells to the tumor microenvironment, thereby enhancing tumor migration and invasion. GPNMB also modulates receptor tyrosine kinases and integrin signaling in a cell autonomous fashion, leading to downstream kinase signaling that in turn triggers the expression and secretion of tumorigenic factors such as matrix metalloproteinases (MMPs) and cytokines. Therefore, GPNMB exerts its pro-tumorigenic role both intracellularly and in a paracrine fashion through shedding its extracellular domain. This review highlights the importance of GPNMB in cancer progression and discusses molecular mediators of GPNMB-induced tumor growth and invasion.
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