Protein tyrosine phosphatase 1B expression contributes to the development of breast cancer

Abstract

Abstract:The protein tyrosine phosphatase 1B (PTP1B) is an important regulator of metabolism. The relationship between PTP1B and tumors is quite complex. The purpose of this study is to explore the expression pattern and role of PTP1B in breast cancer. The expression of PTP1B was detected in 67 samples of breast cancer tissue by Western blot. Cell growth assay, Transwell migration assay, and Scratch motility assay were used to examine the proliferation and migration of MCF-7 with and without PTP1B. The total levels and phosphorylated levels of signal transduction and activator of transcription 3 (STAT3) and the expression of C-C motif chemokine ligand 5 (CCL5) were also examined by Western blot. PTP1B was overexpressed in over 70% of breast cancer tissues, correlating with patients with estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor 2 (HER2)-positive tumors. The data also showed that both tumor size and lymph node metastasis were significantly higher in patients with a higher level of PTP1B. The proliferation and migration of MCF-7 cells were found to be inhibited after knocking down the gene of PTP1B. Our data also showed that PTP1B could up-regulate the dephosphorylated level of STAT3, which could increase the expression of CCL5. These phenomena indicated that PTP1B may play a crucial role in the development of breast cancer.

A STAT3 of Addiction: Adipose Tissue, Adipocytokine Signalling and STAT3 as Mediators of Metabolic Remodelling in the Tumour Microenvironment

“…Signal transducer and activator of transcription 3 (STAT3) activation is counterbalanced by three main groups of negative regulators; phosphatases, Protein Inhibitor of Activated STAT (PIAS) proteins and Suppressor of Cytokine Signalling (SOCS) proteins [70][71][72][73][74]. While phosphatases up-regulated in cancer counteract the JAK-mediated phosphorylation or terminate the activation of STAT3 [70,71,75], PIAS proteins which are upregulated in breast cancer, inhibit STAT3 DNA binding activity [73,76], and SOCS proteins, that inhibit JAK-STAT3 signalling through negative feedback, are downregulated in breast cancer [77]. While the negative regulation actively modulates STAT3 activity, when compromised, it acts to synergistically enhance aberrant stimulation and constitutive activation of STAT3.…”

Drosophila Jak/STAT Signaling: Regulation and Relevance in Human Cancer and Metastasis

“…PTP1B acts a negative regulator of both STAT5 and Jak2 activation in invasive breast cancer cell lines [160]. Breast cancer patients with distant metastases showed high levels of PTP1B protein [161]. Lastly, PIAS has not yet been shown to be a direct Jak/STAT signaling regulator in human breast cancer metastasis, but it is involved in the disease.…”

Vanadium: History, chemistry, interactions with α-amino acids and potential therapeutic applications

“…It is noteworthy that, the inhibition of PTP1B, is carried out both by the direct union of the compounds and the post-translational modifications induced by the reactive oxygen species, the inhibitory process involves the ROS-induced oxidation of cysteine 215 within the active site of PTP1B, so that it abrogates its nucleophilic function [201,202]. The role of PTP1B in cancer has been extensively investigated, recently, it was determined that the increased expression of this enzyme contributes robustly to the development of some types of tumor, especially in breast cancer [203][204]. Vanadium complexes such as oxodiperoxo(1,10-phenanthroline) vanadate (pVphen) [202], oxidovanadium(IV) complexes with oxodiacetate (oda) and 2,2 0 -bipyridyl, (VO(Oda)bipy) and o-phenanthroline (VO-(oda)phen) [193], V(V)-peroxido-betaine [205], Metvan [184] as well as V(III)-L-cysteine [47,188], have shown a close link between antitumor activity and increased production of ROS in various cancer lines.…”