scholarly journals Profiles of PD-1, PD-L1, PD-L2 in Gastric Cancer and Their Relation with Mutation, Immune Infiltration, and Survival

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Jingwei Liu ◽  
Hao Li ◽  
Liping Sun ◽  
Yuan Yuan ◽  
Chengzhong Xing
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cell Adhesion ◽  
Cell Differentiation ◽  
Mononuclear Cell ◽  
Lymphocyte Activation ◽  
Immune Infiltration ◽  
Kegg Pathways ◽  
Coexpressed Genes ◽  
Cell Cell

Background. Although multiple types of cancers demonstrated favorable outcome after immunotherapy of PD-1/PD-L1 blockade, the specific regulatory mechanism of PD genes in gastric cancer (GC) remains largely unknown. Materials and Methods. Expression of RNA, copy number variants, and clinical parameters of GC individuals from TCGA were analyzed. Coexpressed genes for PD-1, PD-L1, and PD-L2 were selected by correlation analysis and confirmed by STRING. Gene Ontology and KEGG pathway analyses were performed by clusterProfiler. The influence of PD-1/PD-L1/PD-L2 on immune cell infiltration was investigated by MCP-counter. Results. PD-L2 demonstrated significant relation with clinical stage of GC (P=0.043). Survival analysis showed that PD-1 expression was correlated with better prognosis of GC patients (HR=0.70, P=0.031), but PD-L2 expression was related with worse survival (HR=1.42, P=0.032). Mutation of PIK3CA could alter the level of PD-1, PD-L1, and PD-L2 (P<0.001), and TP53 mutation demonstrated significant correlation with PD-L1 (P=0.015) and PD-L2 (P=0.014) expression. Enrichment analysis of PD-1/PD-L1/PD-L2 coexpressed genes indicated a biological process of mononuclear cell proliferation, leukocyte cell-cell adhesion, and lymphocyte activation as well as KEGG pathways including cell differentiation of Th1 and Th2, cell differentiation of Th17, and hematopoietic cell landscape. As for immune infiltration analysis, PD-1 was mainly related with cytotoxic lymphocytes and endothelial cells; PD-L1 were associated with monocytic lineage; PD-L2 showed significant correlation with myeloid dendritic cells. Conclusion. PD-1 expression showed association with better prognosis of GC, and PD-L2 expression was related with worse survival. Mutations of PIK3CA and TP53 significantly correlated with PD-1/PD-L1/PD-L2 axis. PD-1/PD-L1/PD-L2 coexpressed genes demonstrated enrichment in mononuclear cell proliferation, leukocyte cell-cell adhesion, and lymphocyte activation as well as KEGG pathways including cell differentiation of Th1, Th2, and Th17.

scholarly journals Prokineticin receptor variants (PKR1-I379V and PKR2-V331M) are protective genotypes in human early pregnancy

Reproduction ◽  
2013 ◽  
Vol 146 (1) ◽  
pp. 63-73 ◽  
Author(s):  
Mei-Tsz Su ◽  
Sheng-Hsiang Lin ◽  
Yi-Chi Chen ◽  
Li-Wha Wu ◽  
Pao-Lin Kuo
Keyword(s):  
Cell Proliferation ◽  
Cell Adhesion ◽  
Intracellular Calcium ◽  
Early Pregnancy ◽  
Calcium Influx ◽  
Recurrent Miscarriage ◽  
Endocrine Gland ◽  
Genotype Frequencies ◽  
Cell Invasiveness ◽  
Cell Cell

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) and its receptor genes (PROKR1(PKR1) andPROKR2(PKR2)) play an important role in human early pregnancy. We have previously shown thatPROKR1andPROKR2are associated with recurrent miscarriage (RM) using the tag-SNP method. In this study, we aimed to identifyPROKR1andPROKR2variants in idiopathic RM patients by genotyping of the entire coding regions. Peripheral blood DNA samples of 100 RM women and 100 controls were subjected to sequence the entire exons ofPROKR1andPROKR2. Significant non-synonymous variant genotypes present in the original 200 samples were further confirmed in the extended samples of 144 RM patients and 153 controls. Genetic variants that were over- or under-represented in the patients were ectopically expressed in HEK293 and JAR cells to investigate their effects on intracellular calcium influx, cell proliferation, cell invasion, cell–cell adhesion, and tube organization. We found that the allele and genotype frequencies ofPROKR1(I379V) andPROKR2(V331M) were significantly increased in the normal control groups compared with idiopathic RM women (P<0.05).PROKR1(I379V) andPROKR2(V331M) decreased intracellular calcium influx but increased cell invasiveness (P<0.05), whereas cell proliferation, cell–cell adhesion, and tube organization were not significantly affected. In conclusion,PROKR1(I379V) andPROKR2(V331M) variants conferred lower risk for RM and may play protective roles in early pregnancy by altering calcium signaling and facilitating cell invasiveness.

A Study of a Mechanism of Cell Proliferation Promotion of Cultured Osteoblasts by Mechanical Vibration

2018 ◽  
Author(s):  
Toshihiko Shiraishi ◽  
Akitoshi Nishijima
Keyword(s):  
Cell Proliferation ◽  
Cell Adhesion ◽  
Cell Division ◽  
Western Blot ◽  
Mechanical Vibration ◽  
Nuclear Fraction ◽  
Analysis Software ◽  
Pile Up ◽  
Western Blot Experiment ◽  
Cell Cell

This paper describes a mechanism of cell proliferation promotion of cultured osteoblasts by mechanical vibration focusing on β-catenin. 12.5 Hz and 0.5 G mechanical vibration was reported to promote the cell proliferation of cultured osteoblasts in plane culture. That is because the mechanical vibration weakens cell-cell adhesion, promotes to pile up cells, and allows cells to form multilayer structure. However, it has not been clarified why cells continue cell division after their monolayer confluent state. Here we show that mechanical vibration not only weakens cell-cell adhesion bound by β-catenin but also promotes to move β-catenin from the cytoplasm to the nuclei, where β-catenin associates with DNA-binding members of the Tcf/LEF family and other associated transcription factors including cell division. After osteoblastic cells were cultured under 12.5 Hz and 0.5 G mechanical vibration, cells were fractionated into nuclear and cytoplasmic fractions using a centrifugation method. β-catenin in each fraction was detected by a western blot experiment. The protein bands from western blot films were quantified with an image processing and analysis software, ImageJ. As a result, the vibration group gave higher expression of β-catenin in nuclear fraction than the non-vibration group just after the vibration group reached the saturated cell density. It indicates that 12.5 Hz and 0.5 G mechanical vibration may promote to move β-catenin into the nuclei and the cell division.

scholarly journals Ajuba, a Cytosolic LIM Protein, Shuttles into the Nucleus and Affects Embryonal Cell Proliferation and Fate Decisions

2000 ◽  
Vol 11 (10) ◽  
pp. 3299-3313 ◽  
Author(s):  
Jyotshnabala Kanungo ◽  
Stephen J. Pratt ◽  
Helene Marie ◽  
Gregory D. Longmore
Keyword(s):  
Cell Proliferation ◽  
Cell Adhesion ◽  
Cell Surface ◽  
Cytosolic Proteins ◽  
Lim Protein ◽  
Receptor Complexes ◽  
Jun Kinase ◽  
Lim Domains ◽  
Endodermal Differentiation ◽  
Cell Cell

Cellular adhesive events affect cell proliferation and differentiation decisions. How cell surface events mediating adhesion transduce signals to the nucleus is not well understood. After cell–cell or cell–substratum contact, cytosolic proteins are recruited to clustered adhesion receptor complexes. One such family of cytosolic proteins found at sites of cell adhesion is the Zyxin family of LIM proteins. Here we demonstrate that the family member Ajuba was recruited to the cell surface of embryonal cells, upon aggregate formation, at sites of cell–cell contact. Ajuba contained a functional nuclear export signal and shuttled into the nucleus. Importantly, accumulation of the LIM domains of Ajuba in the nucleus of P19 embryonal cells resulted in growth inhibition and spontaneous endodermal differentiation. The differentiating effect of Ajuba mapped to the third LIM domain, whereas regulation of proliferation mapped to the first and second LIM domains. Ajuba-induced endodermal differentiation of these cells correlated with the capacity to activate c-Jun kinase and required c-Jun kinase activation. These results suggest that the cytosolic LIM protein Ajuba may provide a new mechanism to transduce signals from sites of cell adhesion to the nucleus, regulating cell growth and differentiation decisions during early development.

Differential expression of cell-cell adhesion proteins and cyclin D in MEK1-transdifferentiated MDCK cells

2000 ◽  
Vol 279 (5) ◽  
pp. C1472-C1482 ◽  
Author(s):  
Ingrid Marschitz ◽  
Judith Lechner ◽  
Irene Mosser ◽  
Martina Dander ◽  
Roberto Montesano ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Adhesion ◽  
Mdck Cells ◽  
Cell Types ◽  
Mek Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Cyclin D ◽  
Invasive Phenotype ◽  
E Cadherin ◽  
Cell Cell

Overexpression of a constitutively active mutant of the mitogen-activated protein kinase kinase MEK1 (caMEK1) in epithelial Madin-Darby canine kidney (MDCK)-C7 cells disrupts morphogenesis, induces an invasive phenotype, and is associated with a reduced rate of cell proliferation. The role of cell-cell adhesion molecules and cell cycle proteins in these processes, however, has not been investigated. We now report loss of E-cadherin expression as well as a marked reduction of β- and α-catenin expression in transdifferentiated MDCK-C7 cells stably expressing caMEK1 (C7caMEK1) compared with epithelial mock-transfected MDCK-C7 (C7Mock1) cells. At least part of the remaining α-catenin was coimmunoprecipitated with β-catenin, whereas no E-cadherin was detected in β-catenin immunoprecipitates. In both cell types, the proteasome-specific protease inhibitors N-acetyl-Leu-Leu-norleucinal (ALLN) and lactacystin led to a time-dependent accumulation of β-catenin, including the appearance of high-molecular-weight β-catenin species. Quiescent as well as serum-stimulated C7caMEK1 cells showed a higher cyclin D expression than epithelial C7Mock1 cells. The MEK inhibitor U-0126 inhibited extracellular signal-regulated kinase phosphorylation and cyclin D expression in C7caMEK1 cells and almost abolished their already reduced cell proliferation rate. We conclude that the transdifferentiated and invasive phenotype of C7caMEK1 cells is associated with a diminished expression of proteins involved in cell-cell adhesion. Although β-catenin expression is reduced, C7caMEK1 cells show a higher expression of U-0126-sensitive cyclin D protein.

scholarly journals Claudins and Gastric Cancer: An Overview

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 290
Author(s):  
Itaru Hashimoto ◽  
Takashi Oshima
Keyword(s):  
Gastric Cancer ◽  
Cell Adhesion ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Treatment Strategies ◽  
The Cancer Genome Atlas ◽  
Therapeutic Drug ◽  
Mesenchymal Transition ◽  
New Treatment ◽  
Cell Cell

Despite recent improvements in diagnostic ability and treatment strategies, advanced gastric cancer (GC) has a high frequency of recurrence and metastasis, with poor prognosis. To improve the treatment results of GC, the search for new treatment targets from proteins related to epithelial–mesenchymal transition (EMT) and cell–cell adhesion is currently being conducted. EMT plays an important role in cancer metastasis and is initiated by the loss of cell–cell adhesion, such as tight junctions (TJs), adherens junctions, desmosomes, and gap junctions. Among these, claudins (CLDNs) are highly expressed in some cancers, including GC. Abnormal expression of CLDN1, CLDN2, CLDN3, CLDN4, CLDN6, CLDN7, CLDN10, CLDN11, CLDN14, CLDN17, CLDN18, and CLDN23 have been reported. Among these, CLDN18 is of particular interest. In The Cancer Genome Atlas, GC was classified into four new molecular subtypes, and CLDN18–ARHGAP fusion was observed in the genomically stable type. An anti-CLDN18.2 antibody drug was recently developed as a therapeutic drug for GC, and the results of clinical trials are highly predictable. Thus, CLDNs are highly expressed in GC as TJs and are expected targets for new antibody drugs. Herein, we review the literature on CLDNs, focusing on CLDN18 in GC.

scholarly journals High extracellular pressure promotes gastric cancer cell adhesion, invasion, migration and suppresses gastric cancer cell differentiation

2016 ◽  
Vol 36 (2) ◽  
pp. 1048-1054 ◽  
Author(s):  
Changlei Su ◽  
Bomiao Zhang ◽  
Wenzhi Liu ◽  
Hongqun Zheng ◽  
Lingyu Sun ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Adhesion ◽  
Cell Differentiation ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Cancer Cell Adhesion

Effects of Mechanical Vibration on Multilayering of Cultured Osteoblasts

2014 ◽  
Author(s):  
Toshihiko Shiraishi ◽  
Akinori Ishii ◽  
Shin Morishita
Keyword(s):  
Cell Proliferation ◽  
Cell Adhesion ◽  
Fluorescent Microscopy ◽  
Mechanical Vibration ◽  
Single Layer ◽  
Control Group ◽  
Fluorescent Staining ◽  
Multilayer Formation ◽  
Cell Cell

This paper describes the mechanism of cell proliferation promotion by mechanical vibration focusing on multilayering of cultured osteoblasts. After osteoblasts were cultured under the mechanical vibration of 0.5 G and 12.5 Hz, the saturated cell density reached approximately twice as high as control. In the vibration group, multilayer formation of osteoblasts was observed by fluorescent microscopy in contrast with almost single layer in the control group. Fluorescent staining demonstrated that the expression of N-cadherin, which plays an important role of cell-cell adhesion, was lower under mechanical vibration than control. Therefore, the application of mechanical vibration to osteoblasts can downregulate the expression of N-cadherin, resulting in weakening of cell-cell adhesion and multilayer formation followed by promotion of cell proliferation.

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