The function of the protein tyrosine phosphatase SHP-1 in cancer

Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worchester, MA 01605, USA.
Gene (Impact Factor: 2.14). 04/2003; 306(1):1-12. DOI: 10.1016/S0378-1119(03)00400-1
Source: PubMed


SHP-1, an SH2 domain-containing protein tyrosine phosphatase, is primarily expressed in hematopoietic cells and behaves as a key regulator controlling intracellular phosphotyrosine levels in lymphocytes. SHP-1 has been proposed as a candidate tumor suppressor gene in lymphoma, leukemia and other cancers, as it functions as an antagonist to the growth-promoting and oncogenic potentials of tyrosine kinase. The decreased levels of SHP-1 protein and SHP-1 mRNA observed in various leukemia and lymphoma cell lines have been attributed to either the methylation of the promoter region of the SHP-1 gene or the post-transcriptional block of SHP-1 protein synthesis. In contrast, SHP-1 protein is normally or over-expressed in some non-lymphocytic cell lines, such as prostate cancer, ovarian cancer and breast cancer cell lines. SHP-1 expression also is decreased in some breast cancer cell lines with negative expression of estrogen receptor as well as some prostate and colorectal cancer cell lines. These data suggest that SHP-1 can play either negative or positive roles in regulating signal transduction pathways. Dysfunction in SHP-1 regulation can cause abnormal cell growth and induce different kinds of cancers. In this paper, we summarize recent studies on the expression and regulation of SHP-1 protein and its pathological function in the development of lymphoma, leukemia and other cancers.

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Available from: Lijun Liu, Oct 02, 2014
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    • "The phosphatase activity of SHP-1 is critically affected by its structural variability. According to the crystal structure studies of ligand-free SHP-1 proteins, SHP-1 forms an auto-inhibited conformation between the N-SH2 domain and the catalytic PTP domain212223. Once the association between N-SH2 and PTP domain is formed, the catalytic function of SHP-1 is significantly inhibited. In this study, we identified the N-SH2 domain as the critical region required for the SHP-1 activation function of dovitinib. "
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    • "It is tempting to speculate that involvement of SHP-1 in pro-apoptotic accumulation of BimEL may play an important role in prevention of malignant transformation and tumorigenicity of various cell types. This would, indeed, go well with the critical role of SHP-1 in tumour suppression and with the frequently observed down-regulation of SHP-1 in various tumours (Delibrias et al., 1997; Wu et al., 2003; Xiao et al., 2009). "
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    • "Notably, SHP-1 has tumor-suppressive potential due to its negative regulation of STAT3 oncogenic signaling during tumor progression [7] [8] [9] [10]. It contains two SH2 domains, a catalytic PTP domain, and a C-terminal tail [10]. "
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