Protein ubiquitination is an important mechanism for regulating the activity and levels of proteins under physiological conditions. Loss of regulation by protein ubiquitination leads to various ...diseases, such as cancer. Two types of enzymes, namely, E1/E2/E3 ligases and deubiquitinases, are responsible for controlling protein ubiquitination. The ubiquitin-specific peptidases (USPs) are the main members of the deubiquitinase family. Many studies have addressed the roles of USPs in various diseases. An increasing number of studies have indicated that USPs are critical for cancer progression, and some USPs have been used as targets to develop inhibitors for cancer prevention. Herein we collect and organize most of the recent studies on the roles of USPs in cancer progression and discuss the development of USP inhibitors for cancer therapy in the future.
Epidermal growth factor receptor (EGFR) expression and activation are the major causes of metastasis in cancers such as head and neck squamous cell carcinoma (HNSCC). However, the reciprocal effect ...of EGF‐induced COX‐2 and angiopoietin‐like 4 (ANGPTL4) on HNSCC metastasis remains unclear. In this study, we revealed that the expression of ANGPTL4 is essential for COX‐2‐derived prostaglandin E2 (PGE2)‐induced tumor cell metastasis. We showed that EGF‐induced ANGPTL4 expression was dramatically inhibited with the depletion and inactivation of COX‐2 by knockdown of COX‐2 and celecoxib treatment, respectively. Prostaglandin E2 induced ANGPTL4 expression in a time‐ and dose‐dependent manners in various HNSCC cell lines through the ERK pathway. In addition, the depletion of ANGPTL4 and MMP1 significantly impeded the PGE2‐induced transendothelial invasion ability of HNSCC cells and the binding of tumor cells to endothelial cells. The induction of molecules involved in the regulation of epithelial‐mesenchymal transition was also dependent on ANGPTL4 expression in PGE2‐treated cells. The depletion of ANGPTL4 further blocked PGE2‐primed tumor cell metastatic seeding of lungs. These results indicate that the EGF‐activated PGE2/ANGPTL4 axis enhanced HNSCC metastasis. The concurrent expression of COX‐2 and ANGPTL4 in HNSCC tumor specimens provides insight into potential therapeutic targets for the treatment of EGFR‐associated HNSCC metastasis.
Metastasis is the major cause of cancer mortality. However, there is no significant improvement in treating advanced head and neck cancer. Our finding indicates that the monitoring levels of angiopoietin‐like 4 (ANGPTL4) are necessary for the treatment of inflammation‐ and/or growth factor‐mediated advanced or metastatic head and neck cancer. The expression of ANGPTL4, a potent angiogenetic factor in cancer, is essential for head and neck cancer metastasis caused by inflammatory response and growth factor stimulation. Therefore, the use of antiinflammatory medicines such as nonsteroidal antiinflammatory drugs and targeting ANGPTL4 could be considered as alternative approaches in treating and preventing the recurrence of head and neck cancer.
Specific protein 1 (Sp1), the first transcription factor to be isolated, regulates the expression of numerous genes involved in cell proliferation, apoptosis, and differentiation. Recent studies ...found that an increase in Sp1 transcriptional activity is associated with the tumorigenesis. Moreover, post-translational modifications of Sp1, including glycosylation, phosphorylation, acetylation, sumoylation, ubiquitination, and methylation, regulate Sp1 transcriptional activity and modulate target gene expression by affecting its DNA binding activity, transactivation activity, or protein level. In addition, recent studies have investigated several compounds with anti-cancer activity that could inhibit Sp1 transcriptional activity. In this review, we describe the effect of various post-translational modifications on Sp1 transcriptional activity and discuss compounds that inhibit the activity of Sp1.
ABSTRACT
Epidermal growth factor receptor (EGFR) activation is a major cause of metastasis in such cancers as head and neck squamous cell carcinoma (HNSCC); however, whether the metabolic enzyme, ...pyruvate dehydrogenase kinase 1 (PDK1), mediates EGF‐enhanced HNSCC metastasis remains unclear. Of interest, we found that EGF induced PDK1 expression in HNSCC. Tumor cell transformation induced by EGF was repressed by PDK1 knockdown, and the down‐regulation of PDK1 expression or inhibition of its activity significantly blocked EGF‐enhanced cell migration and invasion. In addition, depletion of PDK1 impeded EGF‐enhanced binding of HNSCC cells to endothelial cells as well as the metastatic seeding of tumor cells in lungs. PDK1 depletion inhibited EGF‐induced matrix metalloproteinase‐1 (MMP‐1), MMP‐2, MMP‐3, MMP‐9, and fibronectin expression and Rac1/cdc42 activation. Furthermore, PDK1 overexpression induced MMP‐1, MMP‐2, MMP‐3, MMP‐9, and fibronectin expression and Rac1/cdc42 activation. Of interest, depletion of fibronectin inhibited PDK1‐enhanced MMP‐1–3 and MMP‐9 expression as well as Rac1/cdc42 activation and tumor invasion. These results demonstrate that EGF‐induced PDK1 expression enhances HNSCC metastasis via activation of the fibronectin signaling pathway. Inhibition of PDK1 may be a potential strategy for the treatment of EGFR‐mediated HNSCC metastasis.—Hsu, J.‐Y., Chang, J.‐Y., Chang, K.‐Y., Chang, W.‐C., Chen B.‐K. Epidermal growth factor–induced pyruvate dehydrogenase kinase 1 expression enhances head and neck squamous cell carcinoma metastasis via up‐regulation of fibronectin. FASEB J. 31, 4265‐4276 (2017). www.fasebj.org
Graphene is expected to enable superior corrosion protection due to its impermeability and chemical inertness. Previous reports, however, demonstrate limited corrosion inhibition and even corrosion ...enhancement of graphene on metal surfaces. To enable the reliable and complete passivation, the origin of the low inhibition efficiency of graphene was investigated. Combining electrochemical and morphological characterization techniques, nanometer-sized structural defects in chemical vapor deposition grown graphene were found to be the cause for the limited passivation effect. Extremely fast mass transport on the order of meters per second both across and parallel to graphene layers results in an inhibition efficiency of only ∼50% for Cu covered with up to three graphene layers. Through selective passivation of the defects by atomic layer deposition (ALD) an enhanced corrosion protection of more than 99% was achieved, which compares favorably with commercial corrosion protection methods.
G protein‐coupled estrogen receptor‐1 (GPER), a member of the G protein‐coupled receptor (GPCR) superfamily, mediates estrogen‐induced proliferation of normal and malignant breast epithelial cells. ...However, its role in breast cancer stem cells (BCSCs) remains unclear. Here we showed greater expression of GPER in BCSCs than non‐BCSCs of three patient‐derived xenografts of ER−/PR+ breast cancers. GPER silencing reduced stemness features of BCSCs as reflected by reduced mammosphere forming capacity in vitro, and tumor growth in vivo with decreased BCSC populations. Comparative phosphoproteomics revealed greater GPER‐mediated PKA/BAD signaling in BCSCs. Activation of GPER by its ligands, including tamoxifen (TMX), induced phosphorylation of PKA and BAD‐Ser118 to sustain BCSC characteristics. Transfection with a dominant‐negative mutant BAD (Ser118Ala) led to reduced cell survival. Taken together, GPER and its downstream signaling play a key role in maintaining the stemness of BCSCs, suggesting that GPER is a potential therapeutic target for eradicating BCSCs.
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G protein‐coupled estrogen receptor‐1 (GPER) mediates estrogen‐induced proliferation of normal and malignant breast epithelial cells. However, the role of GPER in breast cancer stem cells (BCSC) biology remains unclear. Here, using patient‐derived xenografts of ER–/PR+ breast cancer, the authors found higher expression of GPER in BCSCs than non‐BCSCs. Moreover, the results indicated that stemness features were sustained via GPER‐mediated PKA/BAD phosphorylation. Stimulation by the GPER ligand tamoxifen enhanced BCSC cell viability and population and BAD phosphorylation. The findings revealed a vital role of GPER‐mediated signaling pathways in BCSC survival, suggesting GPER as a potential therapeutic target for eradicating BCSCs.
Glucoregulatory efficiency and ATP production are key regulators for neuronal plasticity and memory formation. Besides its chemotactic and neuroinflammatory functions, the CC chemokine--CCL5 displays ...neurotrophic activity. We found impaired learning-memory and cognition in CCL5-knockout mice at 4 months of age correlated with reduced hippocampal long-term potentiation and impaired synapse structure. Re-expressing CCL5 in knockout mouse hippocampus restored synaptic protein expression, neuronal connectivity and cognitive function. Using metabolomics coupled with FDG-PET imaging and seahorse analysis, we found that CCL5 participates in hippocampal fructose and mannose degradation, glycolysis, gluconeogenesis as well as glutamate and purine metabolism. CCL5 additionally supports mitochondrial structural integrity, purine synthesis, ATP generation, and subsequent aerobic glucose metabolism. Overexpressing CCL5 in WT mice also enhanced memory-cognition performance as well as hippocampal neuronal activity and connectivity through promotion of de novo purine and glutamate metabolism. Thus, CCL5 actions on glucose aerobic metabolism are critical for mitochondrial function which contribute to hippocampal spine and synapse formation, improving learning and memory.
The worldwide flourishing of the Internet of Things (IoT) in the past decade has enabled numerous new applications through the internetworking of a wide variety of devices and sensors. More recently, ...visual sensors have seen their considerable booming in IoT systems because they are capable of providing richer and more versatile information. Internetworking of large-scale visual sensors has been named Internet of Video Things (IoVT). IoVT has its own unique characteristics in terms of sensing, transmission, storage, and analysis, which are fundamentally different from the conventional IoT. These new characteristics of IoVT are expected to impose significant challenges to existing technical infrastructures. In this article, an overview of recent advances in various fronts of IoVT will be introduced and a broad range of technological and system challenges will be addressed. Several emerging IoVT applications will be discussed briefly to illustrate the potentials of IoVT in a broad range of practical scenarios.
Transparent organic upconversion devices are shown in a night‐vision demonstration of a real object under near‐infrared (NIR) illumination in the dark. An extraordinarily high current gain – ...reflecting the on–off switching effect – greater than 15 000 at a driving voltage of 3 V is demonstrated, indicating the high sensitivity to NIR light and potential of using the proposed upconverter in practical applications. A maximum luminance exceeding 1500 cd m−2 at 7 V is achieved. Unlike previous studies, where 2D aperture projection is reported, the current study shows 3D images of real objects under NIR illumination in the dark.
CCAAT/enhancer-binding protein delta (CEBPD) belongs to the CCAAT/enhancer-binding protein family, and these proteins function as transcription factors in many biological processes, including cell ...differentiation, motility, growth arrest, proliferation, cell death, metabolism and immune responses. The functional diversity of CEBPD depends, in part, on the cell type and cellular context, which indicates that CEBPD could interpret a variety of cues to adjust cellular responses in specific situations. Here, we review the regulation of the CEBPD gene and its function in response to inflammatory stimuli. We also address its effects in inflammation-related diseases through a discussion of its recently discovered downstream targets. Regarding to the previous discoveries and new insights in inflammation-associated diseases, suggesting CEBPD could also be a central gene in inflammation. Importantly, the results of this study indicate that the investigation of CEBPD could open a new avenue to help better understand the inflammatory response.
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