Lessard Laurent, Stuible Matthew, Tremblay Michel L
Goodman Cancer Centre and Department of Biochemistry, McGill University, 1160 Pine Avenue, Montréal, Québec, Canada H3G 0B1.
Biochim Biophys Acta. 2010 Mar;1804(3):613-9. doi: 10.1016/j.bbapap.2009.09.018. Epub 2009 Sep 24.
PTP1B is a classical non-transmembrane protein tyrosine phosphatase that plays a key role in metabolic signaling and is a promising drug target for type 2 diabetes and obesity. Accumulating evidence also indicates that PTP1B is involved in cancer, but contrasting findings suggest that it can exert both tumor suppressing and tumor promoting effects depending on the substrate involved and the cellular context. In this review, we will discuss the diverse mechanisms by which PTP1B may influence tumorigenesis as well as recent in vivo data on the impact of PTP1B deficiency in murine cancer models. Together, these results highlight not only the great potential of PTP1B inhibitors in cancer therapy but also the need for a better understanding of PTP1B function prior to use of these compounds in human patients.
蛋白酪氨酸磷酸酶1B(PTP1B)是一种经典的非跨膜蛋白酪氨酸磷酸酶,在代谢信号传导中起关键作用,是2型糖尿病和肥胖症的一个有前景的药物靶点。越来越多的证据还表明PTP1B与癌症有关,但相互矛盾的研究结果表明,根据所涉及的底物和细胞环境,它可以发挥肿瘤抑制和肿瘤促进两种作用。在这篇综述中,我们将讨论PTP1B可能影响肿瘤发生的多种机制,以及最近关于PTP1B缺陷对小鼠癌症模型影响的体内数据。这些结果共同表明,PTP1B抑制剂在癌症治疗中不仅具有巨大潜力,而且在将这些化合物用于人类患者之前,需要更好地了解PTP1B的功能。