Snare-assisted endoscopic resection of gastric subepithelial tumors originating from the muscularis propria layer: a multicenter study.

BACKGROUND AND AIM: Although successful endoscopic resection of gastric subepithelial tumors (SETs) originating from the muscularis propria (MP) layer has been frequently reported, it requires a relatively complicated technique and has a high perforation rate. In this retrospective study, we evaluated the efficacy and safety of the snare-assisted endoscopic resection (SAER) method which is performed using a snare and insulated-tip (IT) knife via a single-channel endoscope to reduce the perforation rate. METHODS: In this study, fifty-six patients with gastric SETs originating from the MP layer treated by the SAER method at three institutions between July 2017 and December 2017 were reviewed. The procedure involved multiple steps as shown in Fig. 2. Data were obtained on demographics, SET features, histopathological diagnoses, procedure time, en bloc resection rate, R0 resection (negative margins) status, and adverse events. RESULTS: Endoscopic resection was successfully performed in all patients. The median overall procedure time was 43.5 min (range 26-106 min). The mean size of resected specimens was 19.73 mm (range 10-33 mm). The overall rate of en bloc resection was 96.4% (54/56). In addition, the perforation rate was 7.1% (4/56), and defects in the stomach wall were very small and easily closed using metallic clips. No postprocedural bleeding occurred in any case. CONCLUSIONS: The SAER method is an effective, safe, less costly technique for the removal of some gastric SETs originating from the MP layer with an appropriate size.

Capn4 is a marker of poor clinical outcomes and promotes nasopharyngeal carcinoma metastasis via nuclear factor-κB-induced matrix metalloproteinase 2 expression.

Calpain small subunit 1 (Capn4) plays a key role in tumor migration or invasion. In this study, expression and function of Capn4 was investigated in human nasopharyngeal carcinoma (NPC). Here we report that both mRNA and protein levels of Capn4 were elevated in NPC tissues when compared to normal NP tissues. Similarly, Capn4 was also highly expressed in multiple NPC cell lines, compared to immortalized human nasopharyngeal epithelial cell line NP69. Moreover, expression of Capn4 was significantly correlated with Epstein-Barr virus infection, advanced stages, and lymph node or distant metastasis (P < 0.001). The patients with NPC displaying higher Capn4 had a significantly shorter overall survival (P = 0.002) and progression-free survival (P = 0.003). Furthermore, siRNA knockdown of Capn4 suppressed cell migration and invasion in vitro and in vivo. These events resulted from Capn4 downregulation were associated with reduced expression of matrix metalloproteinase 2 (MMP2), Snail, and Vimentin. Finally, we demonstrated that Capn4 upregulated MMP2 via nuclear factor-κB (NF-κB) activation, manifested by increased phosphorylation of p65, a subunit of NF-κB. Together, these findings argue a novel function of Capn4 in invasion and metastasis of NPC, and thereby suggest that Capn4 may represent an independent prognostic factor and a potential therapeutic target in NPC.

Overexpression of forkhead box C1 promotes tumor metastasis and indicates poor prognosis in hepatocellular carcinoma.

UNLABELLED: Recurrence and metastasis remain the most common causes of lethal outcomes in hepatocellular carcinoma (HCC) after curative resection. Thus, it is critical to discover the mechanisms underlying HCC metastasis. Forkhead box C1 (FoxC1), a member of the Fox family of transcription factors, induces epithelial-mesenchymal transition (EMT) and promotes epithelial cell migration. However, the role of FoxC1 in the progression of HCC remains unknown. Here, we report that FoxC1 plays a critical role in HCC metastasis. FoxC1 expression was markedly higher in HCC tissues than in adjacent noncancerous tissues. HCC patients with positive FoxC1 expression had shorter overall survival times and higher recurrence rates than those with negative FoxC1 expression. FoxC1 expression was an independent, significant risk factor for recurrence and survival after curative resection. FoxC1 overexpression induced changes characteristic of EMT and an increase in HCC cell invasion and lung metastasis. However, FoxC1 knockdown inhibited these processes. FoxC1 transactivated Snai1 expression by directly binding to the Snai1 promoter, thereby leading to the inhibition of E-cadherin transcription. Knockdown of Snai1 expression significantly attenuated FoxC1-enhanced invasion and lung metastasis. FoxC1 expression was positively correlated with Snai1 expression, but inversely correlated with E-cadherin expression in human HCC tissues. Additionally, a complementary DNA microarray, serial deletion, site-directed mutagenesis, and a chromatin immunoprecipitation assay confirmed that neural precursor cell expressed, developmentally down-regulated 9 (NEDD9), which promotes the metastasis of HCC cells, is a direct transcriptional target of FoxC1 and is involved in FoxC1-mediated HCC invasion and metastasis. CONCLUSIONS: FoxC1 may promote HCC metastasis through the induction of EMT and the up-regulation of NEDD9 expression. Thus, FoxC1 may be a candidate prognostic biomarker and a target for new therapies.

Upregulation of IL-23 expression in patients with chronic hepatitis B is mediated by the HBx/ERK/NF-κB pathway.

IL-23 is a newly discovered proinflammatory cytokine that contributes to the maintenance and expansion of Th17 cells. IL-23 has recently been identified as playing a critical role in a number of chronic inflammatory diseases. However, the regulatory mechanism of IL-23 in chronic hepatitis B (CHB) remains largely unknown. The aims of this study were to detect the expression of IL-23 in CHB patients and to explore the molecular mechanism of hepatitis B virus (HBV)-induced IL-23 expression. Serum levels and hepatic expression of IL-23 were significantly upregulated in CHB patients. A positive correlation was found between IL-23 expression and the histological activity index score, HBV DNA load, and serum alanine aminotransferase and aspartate aminotransferase levels. HBx protein increased IL-23 expression in a dose-dependent manner. It also aided in the nuclear translocation of NF-κB, which directly bound to the promoters of IL-23 subunits p19 and p40 to facilitate their transcription. NF-κB inhibitors blocked the effect of HBx on IL-23 induction, and NF-κB subunits p65 and p50 increased the augmented IL-23 expression. Inhibition of ERK1/2 activation and transfection with ERK dominant-negative plasmid significantly blocked the HBx-induced IL-23 expression. Furthermore, PI3K and Ras-MEK-MAPK inhibitors significantly decreased the ERK1/2 activation and IL-23 expression. Thus, we report a new molecular mechanism for HBV-induced IL-23 expression, which involves the activation of the ERK/NF-κB pathway by HBx, leading to the transactivation of the IL-23 p19 and p40 promoters.

DBC1 is over-expressed and associated with poor prognosis in colorectal cancer.

BACKGROUND: Deleted in breast cancer 1 (DBC1) was initially cloned from a region homozygously deleted in breast cancers, but its role in colorectal cancer remains unknown. The present study aims to examine the expression level of DBC1 and assess its prognostic value in human colorectal cancer. METHODS: Immunohistochemical staining was performed to detect the expression level of DBC1 in a series of 186 colorectal cancer patients. Immunohistochemical staining results were analyzed and compared statistically with various clinicopathological characters and overall survival. RESULTS: Compared with the corresponding non-tumor tissues, a higher expression level of DBC1 was detected in colorectal cancer (P < 0.01). Tissue microarray analysis revealed that DBC1 expression is significantly associated with tumor histological grade, TNM stage and metastatic status (P < 0.01). Importantly, Kaplan-Meier analysis showed that DBC1 expression is associated with shorter overall survival (P < 0.01). Univariate Cox regression suggested that DBC1 expression, poorly differentiation status and the presence of lymph node metastasis predict shorter overall survival in colorectal cancer (P < 0.05). Multivariate Cox regression analysis indicated that DBC1 acts as an independent prognostic factor in colorectal cancer (P < 0.01). CONCLUSIONS: These results suggest that DBC1 is over-expressed in colorectal cancer and that it might serve as a predictor for selecting patients at high risk of poor prognosis.

Classification-Based Evaluation of Multi-Ingredient Dish Using Graphene-Modified Interdigital Electrodes.

A taste sensor with global selectivity can be used to discriminate taste of foods and provide evaluations. Interfaces that could interact with broad food ingredients are beneficial for data collection. Here, we prepared electrochemically reduced graphene oxide (ERGO)-modified interdigital electrodes. The interfaces of modified electrodes showed good sensitivity towards cooking condiments in mixed multi-ingredients solutions under electrochemical impedance spectroscopy (EIS). A database of EIS of cooking condiments was established. Based on the principal component analysis (PCA), subsets of three taste dimensions were classified, which could distinguish an unknown dish from a standard dish. Further, we demonstrated the effectiveness of the electrodes on a typical dish of scrambled eggs with tomato. Our kind of electronic tongue did not measure the quantitation of each ingredient, instead relying on the database and classification algorithm. This method is facile and offers a universal approach to simultaneously identifying multiple ingredients.

Proton-self-doped PANI@CC as the cathode for high-performance aqueous zinc-ion battery.

Aqueous zinc-ion batteries (AZIB) have several advantages such as low cost, large theoretical capacity and good safety. However, the development of polyaniline (PANI) cathode materials has been limited by slow diffusion kinetics. Herein, proton-self-doped polyaniline@carbon cloth (CC) (PANI@CC) was prepared via in-situ polymerization, where polyaniline was deposited on an activated carbon cloth. The PANI@CC cathode exhibits a high specific capacity of 234.3 mA h g-1 at 0.5 A g-1, and excellent rate performance, delivering a capacity of 143 mA h g-1 at 10 A g-1. Furthermore, the reversible redox conversion during the charge-discharge process was studied using ex-situ X-ray photoelectron spectroscopy (XPS) and ex-situ Raman spectra. The results show that the excellent performance of the PANI@CC battery can be attributed to the formation of a conductive network between the carbon cloth and polyaniline. Also, a mixing mechanism involving insertion/extraction of Zn2+/H+ and a double-ion process is proposed. PANI@CC electrode is a novel idea for developing high-performance batteries.

The aMAP Score is an Independent Risk Factor for Intermediate-stage Hepatocellular Carcinoma: A Large Retrospective Cohort Study.

Background: A less effective nomogram for patients with intermediate-stage hepatocellular carcinoma (HCC) to predict overall survival (OS) is available. This study aimed to investigate the role of age-male-albumin-bilirubin-platelet (aMAP) scores in the prognosis of patients with intermediate-stage HCC and develop an aMAP score-based nomogram to predict OS. Methods: Data on newly diagnosed intermediate-stage patients with HCC at Sun Yat-sen University Cancer Center between January 2007 and May 2012 were retrospectively collected. Independent risk factors affecting prognosis were selected by multivariate analyses. The optimal cut-off value for the aMAP score was determined using X-tile. The survival prognostic models were presented by the nomogram. Results: For the 875 patients with intermediate-stage HCC included, the median OS was 22.2 months (95% CI 19.6-25.1). Patients were classified into three groups by X-tile plots (aMAP score < 49.42; 49.42 ≤ aMAP score < 56; aMAP score ≥ 56). Alpha-fetoprotein, lactate dehydrogenase, aMAP score, diameter of main tumor, number of intrahepatic lesions, and treatment regimen were independent risk factors for prognosis. A predicted model was constructed with a C-index of 0.70 (95% CI: 0.68-0.72) in the training goup, and its 1-, 3-, and 5-year area under the receiver operating curve were: 0.75, 0.73, and 0.72. The validation group of the C-index is 0.82. Calibration graphs showed good consistency between the actual and predicted survival rates. The decision curve analysis suggested the clinical utility of the model, which may help clinicians guide clinical decision-making. Conclusion: The aMAP score was an independent risk factor for intermediate-stage HCC. The aMAP score-based nomogram has good discrimination, calibration, and clinical utility.

The TNF-α/ROS/HIF-1-induced upregulation of FoxMI expression promotes HCC proliferation and resistance to apoptosis.

The proliferation-specific transcription factor Forkhead box M1 (FoxM1) acts as a master regulator of cancer cell growth and survival and plays an important role in the development of hepatocellular carcinoma. However, the molecular mechanisms that regulate FoxM1 expression remain largely unknown. In the current study, we demonstrated that tumor necrosis factor (TNF)-αα induced FoxM1 expression and transactivated its promoter activity in hepatoma cells. Serial 5" deletion and site-directed mutagenesis revealed that the induction of FoxM1 expression by TNF-α was dependent upon the hypoxia-inducible factor 1 (HIF1)-1 and HIF1-3/4 binding sites within the FoxM1 promoter. Furthermore, at the transcriptional level, the stabilization of HIF-1α via reactive oxygen species generation led to the binding of HIF-1α to the FoxM1 promoter and resulted in increased FoxM1 expression. The inhibition of both HIF-1α expression and reactive oxygen species generation significantly decreased TNF-α-induced FoxM1 overexpression. Consequently, the upregulation of FoxM1 promoted the proliferation of hepatoma cells and enhanced their resistance to TNF-α-induced apoptosis. Consistently, there was a positive correlation between HIF-1α and FoxM1 expression in 406 human hepatocellular carcinoma tissues, and the combination of these two parameters was a powerful predictor of poor prognosis in hepatocellular carcinoma patients after curative resection. Here, we report a new molecular mechanism by which FoxM1 expression is regulated by the TNF-α/reactive oxygen species/HIF-1 pathway, and this mechanism results in the proliferation of hepatoma cells and their resistance to apoptosis.

Upregulated FoxM1 expression induced by hepatitis B virus X protein promotes tumor metastasis and indicates poor prognosis in hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND & AIMS: Forkhead box M1 (FoxM1) is a master regulator of tumor metastasis that plays an important role in the development of hepatocellular carcinoma (HCC). However, whether or not FoxM1 contributes to the progression of HBV-associated HCC (HBV-HCC) remains unknown. Therefore, we aimed at investigating the clinicopathologic significance of FoxM1 in HBV-HCC and the potential role of FoxM1 in hepatitis B virus X (HBx)-mediated invasiveness and metastasis. METHODS: The expression of FoxM1 and its functional targets matrix metalloproteinase-7 (MMP-7), RhoC, and Rho-kinase 1 (ROCK1) in human HBV-HCC tissues was detected by immunohistochemistry. Luciferase reporter, chromatin immunoprecipitation, and electrophoretic mobility shift assays were used to measure the transcriptional regulation of FoxM1 promoter by HBx. The effect of FoxM1 on HBx-mediated invasiveness and metastasis was analyzed by transwell assays and an orthotopic metastatic model. RESULTS: FoxM1 overexpression correlated with multiple malignant characteristics and indicated poor prognosis of HBV-HCC patients. FoxM1 expression was an independent factor affecting the recurrence and survival of patients with HBV-HCC after surgical resection. FoxM1 promoted hepatoma cell invasion and metastasis by promoting MMP-7, RhoC, and ROCK1 expression, while FoxM1 overexpression was associated with elevated expressions of these proteins in HBV-HCC tissues. HBx upregulated FoxM1 expression through the ERK/CREB pathway, and FoxM1 inhibition significantly decreased HBx-enhanced hepatoma cell invasion in vitro and lung metastasis in vivo. CONCLUSIONS: We report a new molecular mechanism for HBV-associated hepatocarcinogenesis that involves the activation of FoxM1 expression by HBx through the ERK/CREB pathway, thereby leading to invasion and metastasis of hepatoma cells.

Seven DNA Methylation Biomarker Prediction Models for Monitoring the Malignant Progression From Advanced Adenoma to Colorectal Cancer.

Advanced adenoma (AA) holds a significantly increased risk for progression to colorectal cancer (CRC), and we developed a noninvasive DNA methylation prediction model to monitor the risk of AA progression to CRC. We analyzed the differential methylation markers between 53 normal mucosa and 138 CRC tissues, as well as those in cfDNA (cell-free DNA) between 59 AA and 68 early-stage CRC patients. We screened the overlapping markers between tissue DNA and cfDNA for model variables and optimized the selected variables. Then, we established a cfDNA methylation prediction model (SDMBP model) containing seven methylation markers that can effectively discriminate early-stage CRC and AA in the training and validation cohorts, and the AUC (area under the curve) reached 0.979 and 0.918, respectively. Our model also reached high precision (AUC=0.938) in detecting advanced CRC (stage III/IV) and presented better performance than serum CEA and CA199 in screening CRC. The cd-score of the SDMBP model could also robustly predict the TNM stage of CRC. Overall, our SDMBP model can monitor the malignant progression from AA to CRC, and may provide a noninvasive monitoring method for high-risk populations with AA.

Performance Research and Structure Optimization of Labyrinth Screw Pump.

The labyrinth screw pump is a new type of low-flow rotor pump with a simple structure and good sealing performance. It is suitable for the transport of high-viscosity, high-gas-content, and particle-containing media. In this study, a rectangular labyrinth screw pump was used as the research object. The effect of the medium viscosity on the performance of the labyrinth pump was studied through numerical simulations, and the correctness of the simulation method was verified using existing test data. The efficiency and head of the labyrinth screw pump were selected as the optimization objectives, and the pump structural parameters were selected as the optimization parameters. A structural optimization model of the labyrinth screw pump based on response surface theory was established. The structural parameters of the labyrinth pump were reasonably simplified through size correlations, and then parameter sensitivity analysis was performed to determine the important structural parameters that needed to be optimized. The OSFD (optimized space-filling design) was used to combine the optimized parameters and generate the sample space. The response surface theory was combined with a neural network prediction model and a multi-objective genetic algorithm to perform optimization calculations. The results showed that there was an interactive influence between the structural parameters of the stator and rotor of the labyrinth screw pump. Compared with the original model, the optimized model pump had an efficiency increase of 13.55% and a lift increase of 19.53% when conveying a medium with a viscosity of 133 cp.

Terrain-Perception-Free Quadrupedal Spinning Locomotion on Versatile Terrains: Modeling, Analysis, and Experimental Validation.

Dynamic quadrupedal locomotion over rough terrains reveals remarkable progress over the last few decades. Small-scale quadruped robots are adequately flexible and adaptable to traverse uneven terrains along the sagittal direction, such as slopes and stairs. To accomplish autonomous locomotion navigation in complex environments, spinning is a fundamental yet indispensable functionality for legged robots. However, spinning behaviors of quadruped robots on uneven terrain often exhibit position drifts. Motivated by this problem, this study presents an algorithmic method to enable accurate spinning motions over uneven terrain and constrain the spinning radius of the center of mass (CoM) to be bounded within a small range to minimize the drift risks. A modified spherical foot kinematics representation is proposed to improve the foot kinematic model and rolling dynamics of the quadruped during locomotion. A CoM planner is proposed to generate a stable spinning motion based on projected stability margins. Accurate motion tracking is accomplished with linear quadratic regulator (LQR) to bind the position drift during the spinning movement. Experiments are conducted on a small-scale quadruped robot and the effectiveness of the proposed method is verified on versatile terrains including flat ground, stairs, and slopes.

[Comparative analysis on the configuration of vegetative organs of medicinal Chrysanthemum from different original locations and species].

OBJECTIVE: Compared the difference of the configuration of vegetative organs of medicinal Chrysanthemum in the same habitats but from various original locations and species, in order to provide scientific basis for the study of introduction, differentiation within the species, breeding and genetic diversity. METHODS: The experimental plot were divided into some groups randomly in design and the configuration of vegetative organs were observed, measureed and analysed. RESULTS: The differences of the type and shape of the leaves were obvious. All the Chrysanthemum morifolium cv. 'Gongju' had deep notch long-leaves; Chrysanthemum morifolium cv. 'Boju', Chrysanthemum morifolium cv. 'Chuju', Chrysanthemum morifolium cv. 'Hang bai ju' and Chrysanthemum morifolium cv. 'Hang huang ju' had deep notch correctitude-leaves; Chrysanthemum nakingense and Chrysanthemum indicum had long-leaves; Chrysanthemum indicum had clump-leaves. All the 12 medicinal Dendranthema material had auricle except Chrysanthemum morifolium cv. 'Boju' and Chrysanthemum morifolium cv. 'Chuju'. The young leaves of Chrysanthemum morifolium cv. 'Gongju', Chrysanthemum morifolium cv. 'Gongju' and Chrysanthemum morifolium cv. 'Hang bai ju' did not split and the rest were all splitting. CONCLUSION: The differences of the configuration of vegetative organs were obvious and the Key of Vegetative organs was built.

Joule-heated graphene-wrapped sponge enables fast clean-up of viscous crude-oil spill.

The clean-up of viscous crude-oil spills is a global challenge. Hydrophobic and oleophilic oil sorbents have been demonstrated as promising candidates for oil-spill remediation. However, the sorption speeds of these oil sorbents for viscous crude oil are rather limited. Herein we report a Joule-heated graphene-wrapped sponge (GWS) to clean-up viscous crude oil at a high sorption speed. The Joule heat of the GWS reduced in situ the viscosity of the crude oil, which prominently increased the oil-diffusion coefficient in the pores of the GWS and thus speeded up the oil-sorption rate. The oil-sorption time was reduced by 94.6% compared with that of non-heated GWS. Besides, the oil-recovery speed was increased because of the viscosity decrease of crude oil. This in situ Joule self-heated sorbent design will promote the practical application of hydrophobic and oleophilic oil sorbents in the clean-up of viscous crude-oil spills.

Advanced Sorbents for Oil-Spill Cleanup: Recent Advances and Future Perspectives.

Oil sorbents play a very important part in the remediation processes of oil spills. To enhance the oil-sorption properties and simplify the oil-recovery process, various advanced oil sorbents and oil-collecting devices based on them have been proposed recently. Here, we firstly discuss the design considerations for the fabrication of oil sorbents and describe recently developed oil sorbents based on modification strategy. Then, recent advances regarding oil sorbents mainly based on carbon materials and swellable oleophilic polymers are also presented. Subsequently, some additional properties are emphasized, which are required by oil sorbents to cope with oil spills under extreme conditions or to facilitate the oil-collection processes. Furthermore, some oil-collection devices based on oil sorbents that have been developed recently are shown. Finally, an outlook and challenges for the next generation of oil-spill-remediation technology based on oil-sorbents materials are given.

A general chemical transformation route to two-dimensional mesoporous metal selenide nanomaterials by acidification of a ZnSe-amine lamellar hybrid at room temperature.

Two-dimensional inorganic nanomaterials have drawn much attention due to their excellent properties and wide applications associated with unique 2D structures. However, an efficient and versatile chemical synthesis method using ambient conditions for 2D nanomaterials, especially with secondary structures (e.g. mesopores), has still not been reported. Herein, we report a versatile method to synthesize a family of ultrathin and mesoporous nanosheets of metal selenides based on a precursor so-called "red Se remaining Zn" (RSRZ). The principle of our synthesis is based on a template-assisted chemical transformation process via acidification of inorganic-organic hybrid ZnSe(DETA)0.5 nanosheets (DETA: diethylenetriamine). An appropriate amount of acid was added into an aqueous dispersion of ZnSe(DETA)0.5 nanosheets under air for activation. The acidification induced chemical transformation mechanism was studied by tracking the acidification process. This acid controlled reactivity of lamellar hybrids allows it to be possible to capture the highly reactive intermediates, which will provide a new platform for the synthesis of various mesoporous metal selenides.

A Stretchable Electronic Fabric Artificial Skin with Pressure-, Lateral Strain-, and Flexion-Sensitive Properties.

A stretchable and multiple-force-sensitive electronic fabric based on stretchable coaxial sensor electrodes is fabricated for artificial-skin application. This electronic fabric, with only one kind of sensor unit, can simultaneously map and quantify the mechanical stresses induced by normal pressure, lateral strain, and flexion.

Screen-printed microfluidic dielectrophoresis chip for cell separation.

Dielectrophoresis (DEP), the induced motion of polarizable particles in a non-uniform electric field, has been proven as a perfect candidate to transport, accumulate, separate and characterize micro-/nano-scale bioparticles in microfluidic systems. However, conventional fabrication technologies are complex, time-consuming and relatively expensive, leading to low throughput of the DEP-based systems. In this paper, we report a novel microfluidic alternating current DEP (AC-DEP) chip fabricated via inexpensive screen printing method. The innovation of our work consists in the extreme simplicity of the fabrication procedure, i.e., the main components, including electrodes and channels, were constructed by layer-by-layer screen printing process, which is especially suitable for high-throughput mass production. Carbon paste, instead of metals, was used to print interdigitated electrodes with semi-3D structure which not only reduces dramatically the chip cost but also increases particle trapping efficiency. To test the chip performance, yeast cells, as model cells, were trapped and separated from a mixed suspension with PS microspheres. Our results show that high capture rate and separation efficiency can be achieved under optimized conditions.

Activating transcription factor 4 promotes esophageal squamous cell carcinoma invasion and metastasis in mice and is associated with poor prognosis in human patients.

BACKGROUND: Activating transcription factor 4 (ATF4) is a stress response gene that is involved in homeostasis and cellular protection. However, its expression and function in esophageal squamous cell carcinoma (ESCC) remains unknown. In this study, we aimed to determine the clinicopathologic significance of ATF4 in ESCC and its potential role in ESCC invasion and metastasis. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated that ATF4 overexpression is correlated with multiple malignant characteristics and indicates poor prognosis in ESCC patients. ATF4 expression was an independent factor that affected the overall survival of patients with ESCC after surgical resection. ATF4 promoted cell invasion and metastasis by promoting matrix metalloproteinase (MMP)-2 and MMP-7 expression, while its silencing significantly attenuated these activities both in vitro and in vivo. CONCLUSIONS/SIGNIFICANCE: We report that ATF4 is a potential biomarker for ESCC prognosis and that its dysregulation may play a key role in the regulation of invasion and metastasis in ESCC cells. The targeting of ATF4 may provide a new strategy for blocking ESCC metastasis.