scholarly journals Integrin β4 as a Potential Diagnostic and Therapeutic Tumor Marker

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1197
Author(s):  
Haoyu Yang ◽  
Zixuan Xu ◽  
Yuqian Peng ◽  
Jiali Wang ◽  
Yang Xiang

Integrin β4 (ITGβ4) is a class of transmembrane adhesion molecules composed of hemidesmosomes (HDs). Its unique long intracellular domain provides intricate signal transduction functions. These signal transduction effects are especially prominent in tumors. Many recent studies have shown that integrin β4 is differentially expressed in various tumors, and it plays a vital role in tumor invasion, proliferation, epithelial–mesenchymal transition, and angiogenesis. Therefore, we categorize the research related to integrin β4, starting from its structure and function in tumor tissues, and provide a basic description. Based on its structure and function, we believe that integrin β4 can be used as a tumor marker. In clinical practice, it is described as a diagnostic marker for the targeted treatment of cancer and will be helpful in the clinical diagnosis and treatment of tumors.

2016 ◽  
Vol 310 (9) ◽  
pp. L837-L845 ◽  
Author(s):  
Suchita Singh ◽  
Manish Bodas ◽  
Naveen K. Bhatraju ◽  
Bijay Pattnaik ◽  
Atish Gheware ◽  
...  

There is limited knowledge regarding the consequences of hyperinsulinemia on the lung. Given the increasing prevalence of obesity, insulin resistance, and epidemiological associations with asthma, this is a critical lacuna, more so with inhaled insulin on the horizon. Here, we demonstrate that insulin can adversely affect respiratory health. Insulin treatment (1 μg/ml) significantly ( P < 0.05) increased the proliferation of primary human airway smooth muscle (ASM) cells and induced collagen release. Additionally, ASM cells showed a significant increase in calcium response and mitochondrial respiration upon insulin exposure. Mice administered intranasal insulin showed increased collagen deposition in the lungs as well as a significant increase in airway hyperresponsiveness. PI3K/Akt mediated activation of β-catenin, a positive regulator of epithelial-mesenchymal transition and fibrosis, was observed in the lungs of insulin-treated mice and lung cells. Our data suggests that hyperinsulinemia may have adverse effects on airway structure and function. Insulin-induced activation of β-catenin in lung tissue and the contractile effects on ASM cells may be causally related to the development of asthma-like phenotype.


Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 558
Author(s):  
Jin Kyung Seok ◽  
Eun-Hee Hong ◽  
Gabsik Yang ◽  
Hye Eun Lee ◽  
Sin-Eun Kim ◽  
...  

Oxidized phospholipids are well known to play physiological and pathological roles in regulating cellular homeostasis and disease progression. However, their role in cancer metastasis has not been entirely understood. In this study, effects of oxidized phosphatidylcholines such as 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) on epithelial-mesenchymal transition (EMT) and autophagy were determined in cancer cells by immunoblotting and confocal analysis. Metastasis was analyzed by a scratch wound assay and a transwell migration/invasion assay. The concentrations of POVPC and 1-palmitoyl-2-glutaroyl-sn-glycero-phosphocholine (PGPC) in tumor tissues obtained from patients were measured by LC-MS/MS analysis. POVPC induced EMT, resulting in increase of migration and invasion of human hepatocellular carcinoma cells (HepG2) and human breast cancer cells (MCF7). POVPC induced autophagic flux through AMPK-mTOR pathway. Pharmacological inhibition or siRNA knockdown of autophagy decreased migration and invasion of POVPC-treated HepG2 and MCF7 cells. POVPC and PGPC levels were greatly increased at stage II of patient-derived intrahepatic cholangiocarcinoma tissues. PGPC levels were higher in malignant breast tumor tissues than in adjacent nontumor tissues. The results show that oxidized phosphatidylcholines increase metastatic potential of cancer cells by promoting EMT, mediated through autophagy. These suggest the positive regulatory role of oxidized phospholipids accumulated in tumor microenvironment in the regulation of tumorigenesis and metastasis.


2021 ◽  
Vol 20 ◽  
pp. 153303382110330
Author(s):  
Chuangui Chen ◽  
Zhao Ma ◽  
Hongjing Jiang

Epithelial-mesenchymal transition (EMT) is a key step in tumor invasion and distant metastasis. Abundant evidence has documented that exosomes can mediate EMT of tumor cells and endow them with the ability of invasion and migration. However, there are few studies focusing on whether EMT can reverse the secretion of exosomes. In this study, 2 esophageal cancer cells (FLO-1 and SK-GT-4) were selected to compare the migration ability and EMT activation, and to further analyze the secretion ability of exosomes of the 2 cell lines. According to the results, inhibited activation of EMT in FLO-1 cells with relatively high migration ability could effectively reduce the secretion of exosomes. Besides, in SK-GT-4 cells, EMT activation induced by TGF-β could promote the secretion of exosomes. FLO-1 cell derived exosomes exhibited a paracrine effect of promoting the migration of SK-GT-4 cells, and the use of EMT inhibitors could weaken this ability. Furthermore, inhibition of EMT could change the relative content of some miRNAs in exosomes, with a particularly significant downregulation in the expression of miR-196-5p, miR-21-5p and miR-194-5p. Significantly, artificial transfection of the 3 miRNAs into exosomes by electroporation resulted in the recovery of migration-promoting effect of exosomes. Subsequent experiments further revealed that the effect of EMT on these miRNAs could be explained by the intracellular transcription level or the specific sorting mechanism of exosomes. To sum up, our study undoubtedly reveals that EMT has a regulatory effect on exosomes in the quantity and contents in esophageal cancer cells. Significantly, findings in our study provide experimental evidence for the interaction of EMT with the secretion and sorting pathway of exosomes, and also give a new direction for the further study of tumor metastasis.


2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Ricardo Imbroisi Filho ◽  
Alan C. Ochioni ◽  
Amanda M. Esteves ◽  
João G. B. Leandro ◽  
Thainá M. Demaria ◽  
...  

AbstractAmong the principal causative factors for the development of complications related to aging is a diet rich in fats and sugars, also known as the Western diet. This diet advocates numerous changes that might increase the susceptibility to initiate cancer and/or to create a tissue microenvironment more conducive to the growth of malignant cells, thus favoring the progression of cancer and metastasis. Hypercaloric diets in general lead to oxidative stress generating reactive oxygen species and induce endoplasmic reticulum stress. Our results demonstrate that mice bearing tumors fed with a Western diet presented bigger tumor mass with increased insulin sensitivity in these tissues. Several markers of insulin signaling, such as AKT phosphorylation and mTOR pathway, are promoted in tumors of Western diet-fed animals. This process is associated with increased macrophage infiltration, activation of unfolded protein response pathway, and initiation of epithelial–mesenchymal transition (EMT) process in these tumor tissues. Summing up, we propose that the Western diet accelerates the aging-related processes favoring tumor development.


2008 ◽  
Vol 74 (24) ◽  
pp. 7821-7823 ◽  
Author(s):  
Kai Linke ◽  
Nagarajan Periasamy ◽  
Matthias Ehrmann ◽  
Roland Winter ◽  
Rudi F. Vogel

ABSTRACT High hydrostatic pressure (HHP) is suggested to influence the structure and function of membranes and/or integrated proteins. We demonstrate for the first time HHP-induced dimer dissociation of membrane proteins in vivo with Vibrio cholerae ToxR variants in Escherichia coli reporter strains carrying ctx::lacZ fusions. Dimerization ceased at 20 to 50 MPa depending on the nature of the transmembrane segments rather than on changes in the ToxR lipid bilayer environment.


Water ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 3155
Author(s):  
Shumin Liu ◽  
Fengbin Zhao ◽  
Xin Fang

Phytoplankton and bacterioplankton play a vital role in the structure and function of aquatic ecosystems, and their activity is closely linked to water eutrophication. However, few researchers have considered the temporal and spatial succession of phytoplankton and bacterioplankton, and their responses to environmental factors. The temporal and spatial succession of bacterioplankton and their ecological interaction with phytoplankton and water quality were analyzed using 16S rDNA high-throughput sequencing for their identification, and the functions of bacterioplankton were predicted. The results showed that the dominant classes of bacterioplankton in the Qingcaosha Reservoir were Gammaproteobacteria, Alphaproteobacteria, Actinomycetes, Acidimicrobiia, and Cyanobacteria. In addition, the Shannon diversity indexes were compared, and the results showed significant temporal differences based on monthly averaged value, although no significant spatial difference. The community structure was found to be mainly influenced by phytoplankton density and biomass, dissolved oxygen, and electrical conductivity. The presence of Pseudomonas and Legionella was positively correlated with that of Pseudanabaena sp., and Sphingomonas and Paragonimus with Melosira granulata. On the contrary, the presence of Planctomycetes was negatively correlated with Melosira granulata, as was Deinococcus-Thermus with Cyclotella sp. The relative abundance of denitrifying bacteria decreased from April to December, while the abundance of nitrogen-fixing bacteria increased. This study provides a scientific basis for understanding the ecological interactions between bacteria, algae, and water quality in reservoir ecosystems.


2021 ◽  
Author(s):  
Wancheng Zhao ◽  
Lili Yin

Abstract Background: Hypoxia-related genes have been reported to play important roles in a variety of cancers. However, their roles in ovarian cancer (OC) have remained unknown. The aim of our research was to explore the significance of hypoxia-related genes in OC patients.Methods: In this study, 15 hypoxia-related genes were screened from The Cancer Genome Atlas (TCGA) database to group the ovarian cancer patients using the consensus clustering method. Principal component analysis (PCA) was performed to calculate the hypoxia score for each patient to quantify the hypoxic status. Results: The OC patients from TCGA-OV dataset were divided into two distinct hypoxia statuses (cluster.A and cluster.B) based on the expression level of the 15 hypoxia-related genes. Most hypoxia-related genes were expressed more highly in the cluster.A group than in the cluster.B group. We also found that patients in the cluster.A group exhibited higher expression of immune checkpoint-related genes, epithelial-mesenchymal transition-related genes, and immune activation-related genes, as well as elevated immune infiltrates. PCA algorithm indicated that patients in the cluster.A group had higher hypoxia scores than that in in the cluster.B group.Conclusions: In summary, our research elucidated the vital role of hypoxia-related genes in immune infiltrates of OC. Our investigation of hypoxic status may be able to improve the efficacy of immunotherapy for OC.


2019 ◽  
Vol 20 (6) ◽  
pp. 1353 ◽  
Author(s):  
Quan Wang ◽  
Sha Yang ◽  
Shubo Wan ◽  
Xinguo Li

As a secondary messenger, calcium participates in various physiological and biochemical reactions in plants. Photosynthesis is the most extensive biosynthesis process on Earth. To date, researchers have found that some chloroplast proteins have Ca2+-binding sites, and the structure and function of some of these proteins have been discussed in detail. Although the roles of Ca2+ signal transduction related to photosynthesis have been discussed, the relationship between calcium and photosynthesis is seldom systematically summarized. In this review, we provide an overview of current knowledge of calcium’s role in photosynthesis.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Xiaoliang Huang ◽  
Yuting Tao ◽  
Jiamin Gao ◽  
Xianguo Zhou ◽  
Shaomei Tang ◽  
...  

AbstractDysregulation of SUMO modification is linked to carcinogenesis. UBC9 is the sole conjugating enzyme in sumoylation and plays a pivotal role in maintaining homeostasis and restraining stress reactions. However, the clinical significance and function of UBC9 in bladder cancer remain unclear. In this study, immunohistochemistry was used to determine the expression of UBC9. UBC9 knock-down and SUMO inhibition were conducted followed by proliferation, migration, and cell cycle assays. RNA sequencing and bioinformatic analysis were used to identify potential mechanisms of UBC9. Cytokine membrane antibody array was used to detect the expression of cytokine. The mass cytometry TOF (CyTOF) was used to explore the association between bladder cancer stem cell-like population and UBC9 expression. Our results showed that UBC9 played a dual role in bladder cancer. UBC9 was up-regulated in bladder cancer, but was negatively correlated with TNM stage and grade. Knocking-down of UBC9 resulted in dramatic activation of inflammatory gene expression, which might cause inhibition of cell proliferation and inducing cell apoptosis. IL6 was the hub gene in UBC9 regulatory network. Markedly up-regulated IL6 after knocking-down of UBC9 activated the expression of CD44, which was a prominent marker of cancer stem cells. Thus, our results revealed an important and previously undescribed role for UBC9 in modulation of inflammatory signaling of bladder cancer. UBC9 in bladder cancer cells is required to maintain high sumoylation levels and alleviate stress-related inflammation threats to cell survival. Lacking UBC9 contributes to inflammation activation, epithelial–mesenchymal transition and stem cell-like population formation, leading to cancer progression.


2019 ◽  
Vol 17 ◽  
pp. 205873921985889
Author(s):  
Jun Tang ◽  
Jingfang Yang

Epithelial-mesenchymal transition (EMT) is essential for initiation of colorectal cancer (CRC) metastasis, but the diver proteins of EMT remain unclear. Special AT-rich sequence-binding protein 1 (SATB1) was found to be overexpressed in CRC cell lines, and its expression level was positively correlated with CRC progression. Strikingly, EMT process was regulated by SATB1, as SATB1 overexpression upregulated E-cadherin and SATB1 knockdown inhibited N-cadherin cell models. Mechanistically, SATB1 promoted EMT-mediated CRC metastasis via activation of Notch signaling pathway. Taken together, SATB1 plays a vital role in CRC metastasis and may act as a novel prognostic biomarker and a promising therapeutic target for CRC.


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