Studying the role of thrombomodulin-plasminogen interaction in spatial and interfacial invasion of melanoma metastatic progression.

IF 7.7 1区 化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Thi Kim Ngan Ngo, Hua-Lin Wu, Cheng-Hsiang Kuo, Ting-Yuan Tu
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引用次数: 0

Abstract

Thrombomodulin (TM), a transmembrane glycoprotein, has emerged as a key factor in the metastatic spread of various cancers, including malignant melanoma. Despite its recognized significance, the underlying mechanisms of TM's involvement in enhancing metastasis remain incompletely understood. This study addresses this knowledge gap by utilizing spatial and interfacial invasion models in vitro to investigate the effect of the interaction between TM and plasminogen (Plg) on melanoma invasion. While it is well established that Plg induces a chain reaction in the plasmin system, leading to the activation of metalloproteases that promote tumor cell invasion and metastasis, this study is the first to demonstrate that TM binding to Plg can enhance these activations in spatial and interfacial invasion models in vitro. These results highlight the potential of TM as a crucial target for the development of drugs aimed at significantly inhibiting melanoma metastasis and improving patient survival.

研究血栓调节蛋白-血浆蛋白酶相互作用在黑色素瘤转移进展的空间和界面侵袭中的作用。
血栓调节蛋白(TM)是一种跨膜糖蛋白,已成为包括恶性黑色素瘤在内的多种癌症转移扩散的关键因素。尽管其重要性已得到公认,但人们对 TM 参与促进转移的内在机制仍不甚了解。本研究针对这一知识空白,利用体外空间和界面侵袭模型来研究 TM 和纤溶酶原(Plg)之间的相互作用对黑色素瘤侵袭的影响。虽然 Plg 会诱导纤溶酶系统发生连锁反应,导致金属蛋白酶活化,从而促进肿瘤细胞的侵袭和转移,但本研究首次证明了 TM 与 Plg 的结合能在体外的空间和界面侵袭模型中增强这些活化作用。这些结果凸显了 TM 作为关键靶点的潜力,可用于开发旨在显著抑制黑色素瘤转移和提高患者生存率的药物。
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来源期刊
International Journal of Biological Macromolecules
International Journal of Biological Macromolecules 生物-生化与分子生物学
CiteScore
13.70
自引率
9.80%
发文量
2728
审稿时长
64 days
期刊介绍: The International Journal of Biological Macromolecules is a well-established international journal dedicated to research on the chemical and biological aspects of natural macromolecules. Focusing on proteins, macromolecular carbohydrates, glycoproteins, proteoglycans, lignins, biological poly-acids, and nucleic acids, the journal presents the latest findings in molecular structure, properties, biological activities, interactions, modifications, and functional properties. Papers must offer new and novel insights, encompassing related model systems, structural conformational studies, theoretical developments, and analytical techniques. Each paper is required to primarily focus on at least one named biological macromolecule, reflected in the title, abstract, and text.
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