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Fascin actin‐bundling protein 1 (Fascin) is highly expressed in a variety of cancers, including esophageal squamous cell carcinoma (ESCC), working as an important oncogenic protein and promoting the migration and invasion of cancer cells by bundling F‐actin to facilitate the formation of filopodia and invadopodia. However, it is not clear how exactly the function of Fascin is regulated by acetylation in cancer cells. Here, in ESCC cells, the histone acetyltransferase KAT8 catalyzed Fascin lysine 41 (K41) acetylation, to inhibit Fascin‐mediated F‐actin bundling and the formation of filopodia and invadopodia. Furthermore, NAD‐dependent protein deacetylase sirtuin (SIRT) 7‐mediated deacetylation of Fascin‐K41 enhances the formation of filopodia and invadopodia, which promotes the migration and invasion of ESCC cells. Clinically, the analysis of cancer and adjacent tissue samples from patients with ESCC showed that Fascin‐K41 acetylation was lower in the cancer tissue of patients with lymph node metastasis than in that of patients without lymph node metastasis, and low levels of Fascin‐K41 acetylation were associated with a poorer prognosis in patients with ESCC. Importantly, K41 acetylation significantly blocked NP‐G2‐044, one of the Fascin inhibitors currently being clinically evaluated, suggesting that NP‐G2‐044 may be more suitable for patients with low levels of Fascin‐K41 acetylation, but not suitable for patients with high levels of Fascin‐K41 acetylation. © 2024 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

To precisely predict the clinical outcome and determine the optimal treatment options for patients with esophageal squamous cell carcinoma (ESCC) remains challenging. Prognostic models based on multiple molecular markers of tumors have been shown to have superiority over the use of single biomarkers. Our previous studies have identified the crucial role of ezrin in ESCC progression, which prompted us to hypothesize that ezrin-associated proteins contribute to the pathobiology of ESCC. Herein, we explored the clinical value of a molecular model constructed based on ezrin-associated proteins in ESCC patients. We revealed that the ezrin-associated proteins (MYC, PDIA3, and ITGA5B1) correlated with the overall survival (OS) and disease-free survival (DFS) of patients with ESCC. High expression of MYC was associated with advanced pTNM-stage (P=0.011), and PDIA3 and ITGA5B1 were correlated with both lymph node metastasis (PDIA3: P<0.001; ITGA5B1: P=0.001) and pTNM-stage (PDIA3: P=0.001; ITGA5B1: P=0.009). Furthermore, we found that, compared with the current TNM staging system, the molecular model elicited from the expression of MYC, PDIA3, and ITGA5B1 shows higher accuracy in predicting OS (P<0.001) or DFS (P<0.001) in ESCC patients. Moreover, ROC and regression analysis demonstrated that this model was an independent predictor for OS and DFS, which could also help determine a subgroup of ESCC patients that may benefit from chemoradiotherapy. In conclusion, our study has identified a novel molecular prognosis model, which may serve as a complement for current clinical risk stratification approaches and provide potential therapeutic targets for ESCC treatment. [ABSTRACT FROM AUTHOR]

Current staging is inadequate for predicting clinical outcome of esophageal squamous cell carcinoma ( ESCC). Aberrant expression of LOXL2 and actin-related proteins plays important roles in ESCC. Here, we aimed to develop a novel molecular signature that exceeds the power of the current staging system in predicting ESCC prognosis. We found that LOXL2 colocalized with filamentous actin in ESCC cells, and gene set enrichment analysis ( GSEA) showed that LOXL2 is related to the actin cytoskeleton. An ESCC-specific protein-protein interaction ( PPI) network involving LOXL2 and actin-related proteins was generated based on genome-wide RNA-seq in 15 paired ESCC samples, and the prognostic significance of 14 core genes was analyzed. Using risk score calculation, a three-gene signature comprising LOXL2, CDH1, and FN1 was derived from transcriptome data of patients with ESCC. The high-risk three-gene signature strongly correlated with poor prognosis in a training cohort of 60 patients ( P = 0.003). In mRNA and protein levels, the prognostic values of this signature were further validated in 243 patients from a testing cohort ( P = 0.001) and two validation cohorts ( P = 0.021, P = 0.007). Furthermore, Cox regression analysis revealed that the signature was an independent prognostic factor. Compared with using the signature or TNM stage alone, the combined model significantly enhanced the accuracy in evaluating ESCC prognosis. In conclusion, our data reveal that the tumor-promoting role of LOXL2 in ESCC is mediated by perturbing the architecture of actin cytoskeleton through its PPIs. We generated a novel three-gene signature ( PPI interfaces) that robustly predicts poor clinical outcome in ESCC patients. [ABSTRACT FROM AUTHOR]

It is increasingly apparent that cancer development depends not only on genetic alterations, but also on epigenetic changes involving histone modifications. GASC1, member of the histone demethylases affecting heterochromatin formation and transcriptional repression, has been found to be dysregulation in many types of cancers including breast cancer, prostate cancer, metastatic lung sarcomatoid carcinoma, and leukemia. In this study, we examined the expression of GASC1 and certain GASC1-targeted genes (KLF4, MYC, SOX2, PPARG, MDM2, and NANOG) and identified a three-gene prognostic signature (PPARG, MDM2, and NANOG), using risk scores based on immunohistochemical analyses of 149 tumor specimens from patients with esophageal squamous cell carcinoma (ESCC). The presence of a high-risk three-gene signature in the ESCC tumors was significantly associated with decreased overall survival (OS) of the patients. We validated the predictive value of the three-gene signature in a second independent cohort of 101 patients with ESCC in order to determine whether it had predictive value. The results were similar to those in 149 patients. According to multivariate Cox proportional hazards analyses, the predictive model of a three-gene signature was an independent predictor for OS ( p = 0.005 in cohort 1, p = 0.025 in cohort 2). In addition, ROC analysis indicated that the predictive ability of the three-gene model was more robust than that of a single biomarker. Therefore, our three-gene signature is closely associated with OS among patients with ESCC and may serve as a predictor for the poor prognosis of ESCC patients. [ABSTRACT FROM AUTHOR]

In contrast to the well-recognized loss of adherens junctions in cancer progression, the role of desmosomal components in cancer development has not been well explored. We previously demonstrated that desmocollin-2 ( DSC2), a desmosomal cadherin protein, is reduced in oesophageal squamous cell carcinoma ( ESCC), and is associated with enhanced tumour metastasis and poor prognosis. Here, we report that restoration of DSC2 in ESCC cells impeded cell migration and invasion both in vitro and in vivo, whereas siRNA-mediated suppression of DSC2 expression increased cell motility. In E-cadherin-expressing ESCC cells, DSC2 restoration strengthened E-cadherin-mediated adherens junctions and promoted the localization of β-catenin at these junctions, which indirectly inhibited β-catenin-dependent transcription. These effects of DSC2 were not present in EC109 cells that lacked E-cadherin expression. ESCC patients with tumours that had reduced E-cadherin and negative DSC2 had poorer clinical outcomes than patients with tumours that lacked either E-cadherin or DSC2, implying that the invasive potential of ESCC cells was restricted by both DSC2 and E-cadherin-dependent junctions. Further studies revealed that DSC2 was a downstream target of miR-25. Enhanced miR-25 promoted ESCC cell invasiveness, whereas restoration of DSC2 abolished these effects. Collectively, our work suggests that miR-25-mediated down-regulation of DSC2 promotes ESCC cell aggressiveness through redistributing adherens junctions and activating beta-catenin signalling. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A new design of two stacked shorted patch antennas integrated on the same microwave substrate for DCS and WLAN dual-band operations is presented. The two antennas together occupy a small area of 19×28.5 mm2, and the heights for the DCS and WLAN antennas are 10 and 5.2 mm, respectively. Details of the measured antenna performances are presented. © 2001 John Wiley & Sons, Inc. Microwave Opt Technol Lett 30: 134–136, 2001. [ABSTRACT FROM AUTHOR]

A circularly polarized dielectric resonator (DR) antenna array composed of two linearly polarized cylindrical DR antennas with very high permittivity is demonstrated. The cylindrical DR antennas are excited through an annular slot cut in the ground plane of the microstrip feed line. The present design is easy to be implemented, and good circular polarization (CP) performance has also been obtained. ©1999 John Wiley & Sons, Inc. Microwave Opt Technol Lett 21: 323–324, 1999. [ABSTRACT FROM AUTHOR]

The asymmetric unit of the title compound, C(9)H(9)NO(2)·2H(2)O, comprises two independent organic mol-ecules and four water mol-ecules of crystallization. The heterocyclic rings are not planar: in one mol-ecule, the C atom bearing the O atom and the adjacent methyl-ene C atom are displaced by 0.320 (3) and 0.677 (3) Å, respectively, from the other eight atoms of the fused ring system. Equivalent values of 0.243 (3) and 0.659 (3) Å apply to the second mol-ecule. In the crystal, the components are linked by N-H⋯O and O-H⋯O hydrogen bonds, forming a three-dimensional network.

In the title compound, C(26)H(24)Br(2)N(2)O(2), the central naphthalene system carries two Br atoms and two -CH(2)CH(2)NHC(6)H(5) substituents. The phenyl rings of the latter residues are inclined at 74.17 (17) and 51.4 (2)° with respect to the naphthalene ring system. Each alkyl chain adopts a fully extended all-cis conformation with respect to the naphthalene and phenyl rings [N-C-C-O torsion angles = 68.6 (4) and 60.5 (4)°]. In the crystal, one of the N-H groups forms bifurcated N-H⋯(Br,O) hydrogen bonds, which link the mol-ecules into inversion-related dimers. The centrosymmetric dimers are aggregated via pairs of C-H⋯π inter-actions into sheets parallel to (110).