Cubas Rafael, Li Min, Chen Changyi, Yao Qizhi
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Biochim Biophys Acta. 2009 Dec;1796(2):309-14. doi: 10.1016/j.bbcan.2009.08.001. Epub 2009 Aug 14.
Trop2 is a cell-surface glycoprotein overexpressed in a variety of late stage epithelial carcinomas with low to no expression in normal tissues. Some of the important roles that Trop2 plays in epithelial cancers have recently been revealed. Trop2 overexpression is associated with decreased patient survival as well as increased tumor aggressiveness and metastasis. Its overexpression in metastatic tissue makes it a very attractive and potential therapeutic target for late stage disease. This protein can transduce an intracellular calcium signal and contains a conserved phosphatidylinositol 4,5-bisphosphate (PIP(2)) binding motif as well as a serine phosphorylation site which interacts with protein kinase C. This protein has recently being found to be expressed in cells with stem-like properties which allude to a potential role in progenitor cell biology. Further understanding of the signaling pathways involved with this molecule and its important role in metastasis will shed new light on the mechanism of Trop2 overexpression in late stage disease and could result in the development of new therapies targeting this widely overexpressed oncogene.
Trop2是一种细胞表面糖蛋白,在多种晚期上皮癌中过表达,而在正常组织中低表达或不表达。最近揭示了Trop2在上皮癌中发挥的一些重要作用。Trop2过表达与患者生存率降低以及肿瘤侵袭性和转移增加有关。它在转移组织中的过表达使其成为晚期疾病极具吸引力的潜在治疗靶点。这种蛋白质可以转导细胞内钙信号,包含一个保守的磷脂酰肌醇4,5-二磷酸(PIP(2))结合基序以及一个与蛋白激酶C相互作用的丝氨酸磷酸化位点。最近发现这种蛋白质在具有干细胞样特性的细胞中表达,这暗示了它在祖细胞生物学中的潜在作用。对与该分子相关的信号通路及其在转移中的重要作用的进一步了解,将为晚期疾病中Trop2过表达的机制提供新的线索,并可能导致针对这种广泛过表达的癌基因开发新的疗法。