PTPN12 inhibits oral squamous epithelial carcinoma cell proliferation and invasion and can be used as a prognostic marker

Su, Zhe; Tian, Hua; Song, Haiqing; Zhang, Rui; Deng, Anmei; Liu, Hong-Wen

doi:10.1007/s12032-013-0618-4

Cited by 11 publications

(7 citation statements)

References 24 publications

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“…This alteration was more common in TNBC. Likewise, decreased expression of PTPN12 was reported in other human malignancies, including non-small-cell lung carcinoma, esophageal squamous cell carcinoma, nasopharyngeal carcinoma, and hepatocellular carcinoma (18)(19)(20)(21). In all cases, loss of PTPN12 correlated with aggressiveness and poor prognosis.…”

mentioning

confidence: 63%

Loss of PTPN12 Stimulates Progression of ErbB2-Dependent Breast Cancer by Enhancing Cell Survival, Migration, and Epithelial-to-Mesenchymal Transition

Davidson

Souza

et al. 2015

Molecular and Cellular Biology

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e PTPN12 is a cytoplasmic protein tyrosine phosphatase (PTP) reported to be a tumor suppressor in breast cancer, through its capacity to dephosphorylate oncogenic receptor protein tyrosine kinases (PTKs), such as ErbB2. However, the precise molecular and cellular impact of PTPN12 deficiency in breast cancer progression remains to be fully clarified. Here, we addressed this issue by examining the effect of PTPN12 deficiency on breast cancer progression in vivo, in a mouse model of ErbB2-dependent breast cancer using a conditional PTPN12-deficient mouse. Our studies showed that lack of PTPN12 in breast epithelial cells accelerated breast cancer development and lung metastases in vivo. PTPN12-deficient breast cancer cells displayed enhanced tyrosine phosphorylation of the adaptor Cas, the adaptor paxillin, and the kinase Pyk2. They exhibited no detectable increase in ErbB2 tyrosine phosphorylation. PTPN12-deficient cells were more resistant to anoikis and had augmented migratory and invasive properties. Enhanced migration was corrected by inhibiting Pyk2. PTPN12-deficient breast cancer cells also acquired partial features of epithelial-to-mesenchymal transition (EMT), a feature of more aggressive forms of breast cancer. Hence, loss of PTPN12 promoted tumor progression in a mouse model of breast cancer, supporting the notion that PTPN12 is a tumor suppressor in human breast cancer. This function was related to the ability of PTPN12 to suppress cell survival, migration, invasiveness, and EMT and to inhibit tyrosine phosphorylation of Cas, Pyk2, and paxillin. These findings enhance our understanding of the role and mechanism of action of PTPN12 in the control of breast cancer progression. P rotein tyrosine phosphatases (PTPs) play a key role in normal cellular processes, such as proliferation, migration, adhesion, differentiation, and immune cell activation (1-3). Depending on the phosphatase and the cell type, they also have the ability either to suppress or to promote malignant transformation (3). PTPN12, also referred to as PTP-PEST (PTP-proline, glutamic acid, serine, and threonine rich), is a cytoplasmic PTP expressed in a wide spectrum of cell types (4). Studies of PTPN12-deficient mice showed that PTPN12 is a critical positive regulator of migration and adhesion in embryonic fibroblasts, endothelial cells, T cells, macrophages, and dendritic cells (5-11). This function relates to the capacity of PTPN12 to dephosphorylate cytoskeletonassociated substrates such as protein tyrosine kinases (PTKs) Pyk2 and FAK or the adaptors Cas, paxillin, and PSTPIP-1. These substrates are components of the cellular machinery controlling migration and adhesion. PTPN12 can also regulate other substrates, including receptor PTKs, such as ErbB2 and the adaptor . Proteomic data suggested that the ability of PTPN12 to regulate Shc might be critical for conversion of Shc-dependent proliferative signals into migratory signals (15). Several PTPN12 substrates, and in particular, Cas, paxillin, and Shc, also directly associate with PTPN12....

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confidence: 63%

Loss of PTPN12 Stimulates Progression of ErbB2-Dependent Breast Cancer by Enhancing Cell Survival, Migration, and Epithelial-to-Mesenchymal Transition

Davidson

Souza

et al. 2015

Molecular and Cellular Biology

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“…The category of receptor-like phosphatases includes mainly the Receptor-type tyrosine-protein phosphatase delta (PTPRD) [84,85] and the Receptor-type tyrosine-protein phosphatase O (PTPRO) [86] that are enzymatic transmembrane proteins. The inhibiting pSTAT3-Y705 intracellular phosphatases are members of the Protein-tyrosine phosphatase non-receptor (PTPN) family including PTPN1 (or PTP1B) [87] , PTPN2 (or TC-PTP) [88,89] , PTPN6 (or SHP1) [90,91] , PTPN9 (or PTPMeg2) [92,93], PTPN11 (or SHP2) [94] and PTPN12 [95].…”

Section: Stat3 Pathway Down-regulation By Tyrosine Phosphatase Activitymentioning

confidence: 99%

Role of STAT3 in Genesis and Progression of Human Malignant Gliomas

et al. 2016

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Signal transducer and activator of transcription 3 (STAT3) is aberrantly activated in glioblastoma and has been identified as a relevant therapeutic target in this disease and many other human cancers. After two decades of intensive research, there is not yet any approved STAT3-based glioma therapy. In addition to the canonical activation by tyrosine 705 phosphorylation, concordant reports described a potential therapeutic relevance of other post-translational modifications including mainly serine 727 phosphorylation. Such reports reinforce the need to refine the strategy of targeting STAT3 in each concerned disease. This review focuses on the role of serine 727 and tyrosine 705 phosphorylation of STAT3 in glioma. It explores their contribution to glial cell transformation and to the mechanisms that make glioma escape to both immune control and standard treatment.

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“…However, SHP2 suppresses the development of hepatocellular carcinoma by suppressing inflammatory signaling through the STAT3 pathway (65). Likewise, our results show that SHP2 activates the tumor suppressor PTPN12 through ERK signaling, suggesting a tumor-suppressive role for SHP2 through the CD99 signaling axis (66)(67)(68). The influence of the cellular context and tumor microenvironment on the regulation of SHP2's role in tumor progression remains unclear.…”

Section: Discussionmentioning

confidence: 58%

CD99-Derived Agonist Ligands Inhibit Fibronectin-Induced Activation of β1 Integrin through the Protein Kinase A/SHP2/Extracellular Signal-Regulated Kinase/PTPN12/Focal Adhesion Kinase Signaling Pathway

Lee

Kim

Yoo

et al. 2017

Molecular and Cellular Biology

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The human CD99 protein is a 32-kDa glycosylated transmembrane protein that regulates various cellular responses, including cell adhesion and leukocyte extravasation. We previously reported that CD99 activation suppresses ␤1 integrin activity through dephosphorylation of focal adhesion kinase (FAK) at Y397. We explored a molecular mechanism underlying the suppression of ␤1 integrin activity by CD99 agonists and its relevance to tumor growth in vivo. CD99-Fc fusion proteins or a series of CD99-derived peptides suppressed ␤1 integrin activity by specifically interacting with three conserved motifs of the CD99 extracellular domain. CD99CRIII3, a representative CD99-derived 3-mer peptide, facilitated protein kinase A-SHP2 interaction and subsequent activation of the HRAS/RAF1/MEK/ERK signaling pathway. Subsequently, CD99CRIII3 induced FAK phosphorylation at S910, which led to the recruitment of PTPN12 and PIN1 to FAK, followed by FAK dephosphorylation at Y397. Taken together, these results indicate that CD99-derived agonist ligands inhibit fibronectin-mediated ␤1 integrin activation through the SHP2/ERK/PTPN12/FAK signaling pathway.

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PTPN12 inhibits oral squamous epithelial carcinoma cell proliferation and invasion and can be used as a prognostic marker

Cited by 11 publications

References 24 publications

Loss of PTPN12 Stimulates Progression of ErbB2-Dependent Breast Cancer by Enhancing Cell Survival, Migration, and Epithelial-to-Mesenchymal Transition

Loss of PTPN12 Stimulates Progression of ErbB2-Dependent Breast Cancer by Enhancing Cell Survival, Migration, and Epithelial-to-Mesenchymal Transition

Role of STAT3 in Genesis and Progression of Human Malignant Gliomas

CD99-Derived Agonist Ligands Inhibit Fibronectin-Induced Activation of β1 Integrin through the Protein Kinase A/SHP2/Extracellular Signal-Regulated Kinase/PTPN12/Focal Adhesion Kinase Signaling Pathway

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