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Cited by 168Protein Tyrosine PhosphatasesProtein Kinase Regulation and GTPase SignalingCancer Mechanisms and Therapy

Molecular Pathways: Targeting Protein Tyrosine Phosphatases in Cancer

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Bollu, Lakshmi Reddy, Mazumdar, Abhijit, Savage, Michelle I., Brown, Powel H.·2017·Clinical Cancer Research
DOI 10.1158/1078-0432.ccr-16-0934PMC PMC5413367
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Abstract

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.

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  • Loss-of-function as well as gain-of-function mutations and/or overexpression of SHP2 are found in various diseases such as different cancer types, Noonan syndrome, and LEOPARD syndrome.

    “Loss-of-function as well as gain-of-function mutations and/or overexpression of SHP2 are found in various diseases such as different cancer types [49], Noonan- [50], and LEOPARD-syndrome [51].”

    From The tyrosine phosphatase SHP2 increases robustness and information transfer within IL-6-induced JAK/STAT signalling (2021) · cites this paper as [49]

    The cited paper’s “Phosphatases as Oncogenes” section reports SHP2 overexpression in leukemia and breast cancer, and activating SHP2 mutations associated with childhood leukemias. It does not report loss-of-function SHP2 mutations in cancer. The Noonan and LEOPARD syndrome portions of the citing sentence have separate citations and are not judged here. (LLM, conf=0.85)

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Cited by

Sorted by citations

Authors
Bollu, L. R., Mazumdar, A., Savage, M. I., & Brown, P. H.
Affiliations
The University of Texas MD Anderson Cancer Center (US)
Corresponding author
Brown, Powel H.
ORCID
Venue
Clinical Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2017-04-30
Volume
23
Issue
9
Pages
2136-2142
ISSN
  • 1078-0432 (ISSN-L)
  • 1557-3265
DOI
10.1158/1078-0432.ccr-16-0934
PMC
PMC5413367
OpenAlex
W2574246591
Cited by
168
References
4
Citations by year
2026: 14 · 2025: 13 · 2024: 29 · 2023: 26 · 2022: 14 · 2021: 16 · 2020: 21 · 2019: 20 · 2018: 13 · 2017: 2
FWCI
1.43
Type
journal article
Language
en
Open access
Locations
  • Clinical Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
National Cancer Institute (P30CA016672)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cancer Mechanisms and Therapy
Keywords
protein tyrosine phosphatase, cancer, oncogenic signaling, tumor suppressor phosphatase, protein dephosphorylation, PTP inhibitors, cancer therapy, protein kinases, tumor progression
MeSH terms
Humans, Neoplasms, Phosphorylation, Protein Processing, Post-Translational, Signal Transduction, Genes, Tumor Suppressor, Protein Tyrosine Phosphatases, Molecular Targeted Therapy, Carcinogenesis

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