Bollu Lakshmi Reddy, Mazumdar Abhijit, Savage Michelle I, Brown Powel H
Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Clin Cancer Res. 2017 May 1;23(9):2136-2142. doi: 10.1158/1078-0432.CCR-16-0934. Epub 2017 Jan 13.
The aberrant activation of oncogenic signaling pathways is a universal phenomenon in cancer and drives tumorigenesis and malignant transformation. This abnormal activation of signaling pathways in cancer is due to the altered expression of protein kinases and phosphatases. In response to extracellular signals, protein kinases activate downstream signaling pathways through a series of protein phosphorylation events, ultimately producing a signal response. Protein tyrosine phosphatases (PTP) are a family of enzymes that hydrolytically remove phosphate groups from proteins. Initially, PTPs were shown to act as tumor suppressor genes by terminating signal responses through the dephosphorylation of oncogenic kinases. More recently, it has become clear that several PTPs overexpressed in human cancers do not suppress tumor growth; instead, they positively regulate signaling pathways and promote tumor development and progression. In this review, we discuss both types of PTPs: those that have tumor suppressor activities as well as those that act as oncogenes. We also discuss the potential of PTP inhibitors for cancer therapy. .
致癌信号通路的异常激活是癌症中的普遍现象，驱动肿瘤发生和恶性转化。癌症中信号通路的这种异常激活是由于蛋白激酶和磷酸酶表达的改变。响应细胞外信号，蛋白激酶通过一系列蛋白质磷酸化事件激活下游信号通路，最终产生信号反应。蛋白酪氨酸磷酸酶（PTP）是一类能从蛋白质上水解去除磷酸基团的酶。最初，PTP被证明可作为肿瘤抑制基因，通过使致癌激酶去磷酸化来终止信号反应。最近，越来越清楚的是，几种在人类癌症中过表达的PTP并不抑制肿瘤生长；相反，它们正向调节信号通路并促进肿瘤发展和进展。在这篇综述中，我们讨论了两种类型的PTP：具有肿瘤抑制活性的PTP以及充当癌基因的PTP。我们还讨论了PTP抑制剂在癌症治疗中的潜力。
