IntroductionSignal transducer and activator of transcription 3 (STAT3) is over-activated or phosphorylated in breast cancers. The hyper-phosphorylation of STAT3 was attributed to either up-regulated phosphorylation by several tyrosine-kinases or down-regulated activity of phosphatases. Although several factors have been identified to phosphorylate STAT3, it remains unclear how STAT3 is dephosphorylated by PTPMeg2. The aim of this study was to determine the role of PTPMeg2 as a phosphatase in regulation of the activity of STAT3 in breast cancers.MethodsImmunoprecipitation assays were used to study the interaction of STAT3 with PTPMeg2. A series of biochemistry experiments were performed to evaluate the role of PTPMeg2 in the dephosphorylation of STAT3. Two breast cancer cell lines MCF7 (PTPMeg2 was depleted as it was endogenously high) and MDA-MB-231 (PTPMeg2 was overexpressed as it was endogenously low) were used to compare the level of phosphorylated STAT3 and the tumor growth ability in vitro and in vivo. Samples from breast carcinoma (n = 73) were subjected to a pair-wise Pearson correlation analysis for the correlation of levels of PTPMeg2 and phosphorylated STAT3.ResultsPTPMeg2 directly interacts with STAT3 and mediates its dephosphorylation in the cytoplasm. Over-expression of PTPMeg2 decreased tyrosine phosphorylation of STAT3 while depletion of PTPMeg2 increased its phosphorylation. The decreased tyrosine phosphorylation of STAT3 is coupled with suppression of STAT3 transcriptional activity and reduced tumor growth in vitro and in vivo. Levels of PTPMeg2 and phosphorylated STAT3 were inversely correlated in breast cancer tissues (P = 0.004).ConclusionsPTPMeg2 is an important phosphatase for the dephosphorylation of STAT3 and plays a critical role in breast cancer development.
Background: IRS1/2 is a critical component of insulin signaling, but it remains unclear whether IRS1/2 functions on Wnt signaling. Results: IRS1/2 interacts with and stabilizes Dvl2 by suppressing its autophagic degradation, leading to promotion of Wntmediated EMT and cell proliferation. Conclusion: IRS1/2 positively regulates Wnt/-catenin signaling through Dvl2. Significance: The IRS1/2-Dvl2 node might be implicated in tumorigenesis and metastasis.
Gastric cancer, like most of other cancers, has an uncontrolled cell cycle regulated by cyclins and cyclin-dependent kinases (CDKs). In this study, we reported that gastric cancer cells showed an accelerated G2/M transition promoted by CREPT/RPRD1B and Aurora kinase B (Aurora B). We found that CREPT/RPRD1B and Aurora B were coordinately expressed during the cell cycle in gastric cancer cells. Deletion of CREPT/RPRD1B disturbed the cell progression and extended the length of cell cycle, leading to a significant accumulation of mitotic cells. Mechanistically, we revealed that CREPT/RPRD1B interacted with Aurora B to regulate the expression of Cyclin B1 in gastric cancer cells. Interestingly, Aurora B phosphorylates S145 in a well-conserved motif of CREPT/RPRD1B. We proposed that phosphorylation of CREPT/RPRD1B by Aurora B is required for promoting the transcription of Cyclin B1, which is critical for the regulation of gastric tumorigenesis. Our study provides a mechanism by which gastric tumor cells maintain their high proliferation rate via coordination of Aurora B and CREPT/RPRD1B on the expression of Cyclin B1. Targeting the interaction of Aurora B and CREPT/RPRD1B might be a strategy for anti-gastric cancer therapy in the future.
Nrf2 (NFE2L2) is a transcription factor belonging to the Cap'N'Collar subfamily of basic-leucine zipper (bZIP) family of transcription factors, which plays a significant role in adaptive responses to oxidative stress. To investigate the relationship of between the mutation of Nrf2 gene and non-small cell lung cancer (NSCLC), in this study, we sequenced the Nrf2 gene from a total of 103 patients with NSCLC and corresponding blood samples. It is found that there is a discordance of Nrf2 mutations between NSCLC and corresponding blood samples. These differences may indicate that the variants in the Nrf2 gene are associated with an increased risk for lung cancer. In addition, the factor of smoking status is observed to play important roles in triggering the occurrence of the disorder.
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