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. 2017 May 1;23(9):2136-2142.
doi: 10.1158/1078-0432.CCR-16-0934. Epub 2017 Jan 13.

Molecular Pathways: Targeting Protein Tyrosine Phosphatases in Cancer

Free PMC article

Molecular Pathways: Targeting Protein Tyrosine Phosphatases in Cancer

Lakshmi Reddy Bollu et al. Clin Cancer Res. .
Free PMC article


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. Clin Cancer Res; 23(9); 2136-42. ©2017 AACR.

Conflict of interest statement

Conflict of interest: PH Brown is on the Scientific Advisory Board of Susan G. Komen for the Cure. All remaining authors declare no actual, potential, or perceived conflict of interest that would prejudice the impartiality of this article.


Figure 1
Figure 1
Targeting molecular pathway. Activation of oncogenic PTPs, (SHP2, PTP1B and PTP4A3) by growth factor receptors promotes tumorigenesis, growth, survival and metastasis through activating Ras/raf/MAPK and PI3K/Akt pathways in several human cancers. Targeting these phosphatases reduces the tumor formation, growth, survival and metastatic potential.

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