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. 2015 Feb;34(2):61-9.
doi: 10.5732/cjc.014.10146. Epub 2014 Oct 17.

Receptor-type Protein Tyrosine Phosphatases in Cancer

Free PMC article

Receptor-type Protein Tyrosine Phosphatases in Cancer

Yu Du et al. Chin J Cancer. .
Free PMC article


Protein tyrosine phosphatases (PTPs) play an important role in regulating cell signaling events in coordination with tyrosine kinases to control cell proliferation, apoptosis, survival, migration, and invasion. Receptor-type protein tyrosine phosphatases (PTPRs) are a subgroup of PTPs that share a transmembrane domain with resulting similarities in function and target specificity. In this review, we summarize genetic and epigenetic alterations including mutation, deletion, amplification, and promoter methylation of PTPRs in cancer and consider the consequences of PTPR alterations in different types of cancers. We also summarize recent developments using PTPRs as prognostic or predictive biomarkers and/or direct targets. Increased understanding of the role of PTPRs in cancer may provide opportunities to improve therapeutic approaches.


Figure 1.
Figure 1.. Receptor-type protein tyrosine phosphatase (PTPR) genetic alterations in cancer.
Three genetic mechanisms were reported in the Cancer Genome Atlas (TCGA): mutation (green), deletion (blue), and amplification (red). Alterations of 20 PTPR family members are summarized across 25 human cancers studied to date (all TCGA, provisional), including skin cutaneous melanoma, lung adenocarcinoma, gastric adenocarcinoma, bladder urothelial carcinoma, lung squamous cell carcinoma, uterine corpus endometrial carcinoma, sarcoma, colorectal adenocarcinoma, ovarian serous cystadenocarcinoma, head and neck squamous cell carcinoma, prostate adenocarcinoma, uterine carcinosarcoma, breast invasive carcinoma, adrenocortical carcinoma, cervical squamous cell carcinoma and endocervical adenocarcinoma, glioblastoma multiforme, renal papillary cell carcinoma, lymphoid neoplasm diffuse large B-cell lymphoma, renal chromophobe, hepatocellular carcinoma, acute myeloid leukemia, pancreatic adenocarcinoma, brain lower grade glioma, renal clear cell carcinoma, and thyroid carcinoma. Ratios were generated using the number of cases altered by each mechanism divided by the total number of cases examined in each cancer that contain the specific alteration.
Figure 2.
Figure 2.. Protein tyrosine phosphatase receptor type R (PTPRR) amplification is associated with PTPRR overexpression in lung adenocarcinoma, melanoma, and sarcoma.
Unpaired t test was used to compare RNAseq values of TCGA samples with and without copy number changes (CNA), namely, 12 lung adenocarcinoma samples with PTPRR amplification and 126 samples without copy number alteration, 11 melanoma samples with amplification and 231 without copy number alteration, and 19 sarcoma samples with amplification and 53 without copy number alteration. PTPRR mRNA levels were higher in lung adenocarcinomas, melanomas, and sarcomas with amplification compared with those without copy number alterations (respectively, P = 0.0009, P < 0.0001, P = 0.0428).

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