Transforming growth factor β (TGF‑β) is a polypeptide growth factor with various biological activities, and is widely distributed in various tissues. In mammals, TGF‑β has three isoforms: TGF‑β1, 2, ...and 3, of which TGF‑β1 is most abundant in the TGF‑β family. TGF‑β1 is closely related to the occurrence and development of tumors. A large number of previous studies have shown that melatonin can inhibit a variety of malignancies. Thus, the aim of the present study was to investigate the role of TGF‑β1 in the melatonin‑mediated inhibition of the proliferation of gastric cancer cells in vitro and in vivo. TGF‑β1 cytokine stimulation, anti‑TGF‑β1 neutralizing antibody blocking, siRNA TGF‑β1 and other means were utilized to explore the role of TGF‑β1 during the course of anti‑gastric cancer by melatonin. The results showed that melatonin upregulated the expression of TGF‑β1 in tumor tissues during the process of inhibiting gastric cancer tumor growth in vivo. Melatonin inhibited the proliferation of gastric cancer cells in vitro, accompanied by increased expression of TGF‑β1 in a time‑dependent manner. siRNA‑mediated silencing of TGF‑β1 and anti‑TGF‑β1 neutralizing antibody completely blocked the TGF‑β1 pathway, which significantly antagonized the melatonin‑mediated inhibition of the growth and proliferation of gastric cancer cells, and promoted G1 phase to S phase transformation of MFC cells. Our findings suggest that TGF‑β1 is involved in the regulation of the proliferation of tumor cells. One of the ways in which melatonin inhibits the proliferation of gastric cancer cells is dependent on the TGF‑β1 signaling pathway.
ADAS and autonomous driving are booming. As technologies continue to innovate and mature, whether travelers understand, accept, and buy them will directly impact the technological development, ...popularization, and profitability of these products. This study analyzes the influence of urban residents’ personal, family, and commuting characteristics on their willingness to choose and pay for ADAS and autonomous driving functions. Using the questionnaire survey data for Jiading and Meishan in China, Logit models are established for willingness to choose, and linear regression models are established for willingness to pay. Although Jiading and Meishan are similar in terms of city size and population, there are some differences in the influencing factors for willingness to choose and pay because of the differences in industrial structure, city culture, and residents’ commuting habits. The results show that significant influencing factors vary for different levels of ADAS and autonomous driving functions. The findings of this research can provide a reference for city authorities, designers, and sellers of ADAS products or autonomous vehicles to identify potential buyers and promote related products.
Desmosomes are intercellular adhesion complexes involved in various aspects of epithelial pathophysiology, including tissue homeostasis, morphogenesis, and disease development. Recent studies have ...reported that the abnormal expression of various desmosomal components correlates with tumor progression and poor survival. In addition, desmosomes have been shown to act as a signaling platform to regulate the proliferation, invasion, migration, morphogenesis, and apoptosis of cancer cells. The occurrence and progression of head and neck cancer (HNC) is accompanied by abnormal expression of desmosomal components and loss of desmosome structure. However, the role of desmosomal components in the progression of HNC remains controversial. This review aims to provide an overview of recent developments showing the paradoxical roles of desmosomal components in tumor suppression and promotion. It offers valuable insights for HNC diagnosis and therapeutics development.
L1 cell adhesion molecule (L1CAM) is highly expressed in various types of human cancers, displaying yet unknown molecular mechanisms underlying their oncogenic potential. Here, we found that L1CAM ...expression was significantly increased in esophageal squamous cell carcinoma (ESCC;
n
= 157) lesions compared with non-cancerous tissues. High tumorous L1CAM expression significantly correlated with reduced overall survival. Experimentally, L1CAM knockdown led to decreased cell growth, migration, and invasiveness in vitro, whereas overexpression of L1CAM showed the opposite effect. In nude mice, L1CAM depletion attenuated tumorigenesis and ability to penetrate the tissues surrounding ESCC cells. Gene set enrichment analysis (GSEA) and SubpathwayMiner analysis on gene expression profiles (microarray data on ESCC tissues, GSE53625; cDNA microarray data on L1CAM-knockdown ESCC cell line, GSE86268) suggested that L1CAM-co-expression genes were related to cell motility, cell proliferation, and regulation of actin cytoskeleton, validating the above experimental findings. Further mechanistical analysis showed that L1CAM upregulated the expression of the cytoskeletal protein ezrin via activating integrin β1/MAPK/ERK/AP1 signaling and thus led to the malignant phenotypes of ESCC cells. Together, our findings suggest that L1CAM may be employed as a valuable prognosis marker and a therapeutic target for ESCC patients and that L1CAM promotes ESCC tumorigenicity by upregulating ezrin expression.
Key messages
L1CAM promotes growth and invasiveness of ESCC cells in vitro and in vivo.
L1CAM upregulates the expression of ezrin by integrin α5β1/MAPK/ERK/AP1 pathway.
Ezrin is a key downstream effector in the L1CAM-promoted malignant phenotypes.
High expression levels of both L1CAM and ezrin significantly correlated with reduced overall survival.
Nuclear L1CAM is an independent prognosis marker for esophageal squamous cell carcinoma.
The following review highlights pH shock, a novel environmental factor, as a tool for the improvement of fermentation production. The aim of this review is to introduce some recent original studies ...on the enhancement of microbial fermentation production by pH shock. Another purpose of this review is to improve the understanding of the processes that underlie physiological and genetic differences, which will facilitate future research on the improvement of fermentation production and reveal the associated molecular mechanisms. This understanding will simultaneously promote the application of this strategy to other microbial fermentation systems. Furthermore, improvement of the cellular tolerance of genetically engineered bacteria can also be a new field of research in the future to enhance fermentation production.
Objective:
Colorectal cancer is one of the most important malignant cancer in the world with high incidence and mortality. Some studies have found that the expression of low serum L1 cell adhesion ...molecule is associated with poor prognosis in some malignancies. It is suggested that L1 cell adhesion molecule is a candidate serum marker for certain tumors. However, the relationship between serum L1 cell adhesion molecule and colorectal cancer, especially about the diagnostic value, is rarely reported. Therefore, this study aimed to evaluate the diagnostic potential of serum L1 cell adhesion molecule in patients with colorectal cancer.
Methods:
Enzyme-linked immunosorbent assay was carried out to detect L1 cell adhesion molecule level in sera of 229 patients with colorectal cancer and 145 normal controls. Receiver operating characteristic curves were employed to calculate the accuracy of diagnosis.
Results:
The levels of serum L1 cell adhesion molecule in the colorectal cancer group were significantly lower than that in normal controls (P < .05). In the normal group, the area under the receiver operating characteristic curve (area under the curve) of all colorectal cancer was 0.781 (95% confidence interval: 0.734-0.828) and early-stage colorectal cancer was 0.764 (95% confidence interval: 0.705-0.823). With optimized cutoff of 17.760 ng/mL, L1 cell adhesion molecule showed certain diagnostic value with specificity of 90.3% and sensitivities of 43.2% and 36.2% in colorectal cancer and early-stage colorectal cancer, respectively. Clinical data analysis showed that the levels of L1 cell adhesion molecule were significantly correlated with gender (P < .05) and early and late stages (P < .05). Furthermore, when compared with carcinoembryonic antigen, serum L1 cell adhesion molecule had significantly improved diagnostic accuracy for both colorectal cancer and early-stage colorectal cancer.
Conclusions:
Our study demonstrated that serum L1 cell adhesion molecule might be served as a potential biomarker for the diagnosis of colorectal cancer.
Esophagogastric junction tumor (EGJ) is a rare but fatal disease with a rapid rising incidence worldwide in the late 20 years, and it lacks a convenient and safe method for diagnosis. The present ...study aimed to evaluate the potential of serum CYR61 as a biomarker for the diagnosis of EGJ tumor.
Enzyme-linked immunosorbent assay (ELISA) was used to estimate CYR61 levels in sera of 152 EGJ tumor patients and 137 normal controls. Receiver operating characteristics (ROC) was carried out to evaluate the diagnostic accuracy. The Mann-Whitney's U test was used to compare the difference of serum levels of CYR61 between groups. And chi-square tests were employed to estimate the correlation of the positive rate of serum CYR61 between/among subgroups.
Serum CYR61 levels were statistically lower in EGJ tumor and early-stage EGJ tumor patients than those in normal controls (P<0.0001). The sensitivity, specificity and the area under the curve (AUC) of this biomarker in EGJ tumor were 88.2%, 43.8% and 0.691, respectively, and those for early stage of EGJ tumor were 80.0%, 66.4% and 0.722, respectively. Analyses showed that there was no correlation between the clinical data and the levels of CYR61 (P>0.05).
The present study showed that CYR61 might be a potential biomarker to assist the diagnosis of EGJ tumor.
Lipocalin 2 (LCN2) is a poor prognostic factor in esophageal squamous cell carcinoma (ESCC), however its functional roles and molecular mechanisms of action remain to be clarified. Here, we described ...the functions and signaling pathways for LCN2 in ESCC. Overexpression of LCN2 in ESCC cells accelerated cell migration and invasion in vitro, and promoted lung metastasis in vivo. Blocking LCN2 expression inhibited its pro-oncogenic effect. Either overexpression of LCN2 or treatment with recombinant human LCN2 protein enhanced the activation of MEK/ERK pathway, which in turn increases endogenous LCN2 to increase MMP-9 activity. The decreased p-cofilin and increased p-ERM induced by pERK1/2 cause the cytoskeleton F-actin rearrangement and alter the behavior of ESCC cells mediated by LCN2. As a consequence, activation of MMP-9 and the rearrangement of F-actin throw light on the mechanisms for LCN2 in ESCC. These results imply that LCN2 promotes the migration and invasion of ESCC cells through a novel positive feedback loop.
•LCN2 promotes the migration and invasion of esophageal squamous cell carcinoma cells both in vitro and in vivo.•LCN2 increases MMP-9 and phospho-ERM (phospho-ezrin/radixin/moesin) and decreases phospho-cofilin.•LCN2 causes the cytoskeleton F-actin rearrangement in esophageal squamous cell carcinoma cells.•This promotion is through a novel positive feedback loop mediated by ERK1/2 pathway.
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