Tumor-Associated Macrophage-Derived Exosomes Promote the Progression of Gastric Cancer by Regulating the P38MAPK Signaling Pathway and the Immune Checkpoint PD-L1

Colorectal cancer (CRC) remains the third most commonly diagnosed cancer, ranking second among the most common causes of cancer-related mortality. Immune checkpoint therapy has recently been shown to have great potential. However, only some patients respond to immune checkpoint blockade, indicating the unmet need for determining the underlying mechanism of colorectal cancer immunosuppression. In this study, we analyzed The Cancer Genome Atlas (TCGA) datasets and found that high expression of PIPKIγ positively correlated with tumor-associated macrophage infiltration. Further loss-of-function studies revealed that silencing PIPKIγ greatly reduced CCL2 expression at both the mRNA and protein levels, leading to weak chemotaxis of cancer cells to macrophages. Mechanistically, PIPKIγ facilitated PI3K-Akt-mTOR signaling pathway activation to increase STAT3 phosphorylation levels, thus triggering CCL2 transcription to enhance tumor-associated macrophage recruitment. These findings identify the PIPKIγ signaling pathway as a new actor in colorectal cancer immunosuppression and a potential therapeutic target for this common cancer.

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The Effect of α1, 2-Fucosyl Transferase Gene Transfection on p38MAPK Signaling Pathway-mediated Apoptosis of Ovarian Carcinoma RMG-I Cells*

PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS ◽

10.3724/sp.j.1206.2009.00459 ◽

2010 ◽

Vol 37 (2) ◽

pp. 175-183 ◽

Cited By ~ 4

Author(s):

Jian-Ping CONG ◽

Bei LIN ◽

Juan-Juan LIU ◽

Qing LIU ◽

Fei-Fei LI ◽

...

Keyword(s):

Ovarian Carcinoma ◽

Signaling Pathway ◽

Gene Transfection ◽

Transferase Gene ◽

P38mapk Signaling ◽

I Cells

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Bioinformatics Analysis Identifies CPZ as a Tumor Immunology Biomarker For Gastric Cancer

Current Bioinformatics ◽

10.2174/1574893615999200707145643 ◽

2020 ◽

Vol 15 ◽

Author(s):

Yuan Gu ◽

Ying Gao ◽

Xiaodan Tang ◽

Huizhong Xia ◽

Kunhe Shi

Keyword(s):

Gastric Cancer ◽

T Cells ◽

Signaling Pathway ◽

Tumor Immunology ◽

Bioinformatics Analysis ◽

Human Cancer ◽

Disease Free Survival ◽

Kaplan Meier ◽

Potential Biomarker ◽

Pathway Regulation

Background: Gastric cancer (GC) is one of the most common malignancies worldwide. However, the biomarkers for the prognosis and diagnosis of Gastric cancer were still need. Objective: The present study aimed to evaluate whether CPZ could be a potential biomarker for GC. Method: Kaplan-Meier plotter (http://kmplot.com/analysis/) was used to determine the correlation between CPZ expression and overall survival (OS) and disease-free survival (DFS) time in GC [9]. We analyzed CPZ expression in different types of cancer and the correlation of CPZ expression with the abundance of immune infiltrates, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells, via gene modules using TIMER Database. Results: The present study identified that CPZ was overexpressed in multiple types of human cancer, including Gastric cancer. We found that overexpression of CPZ correlates to the poor prognosis of patients with STAD. Furthermore, our analyses show that immune infiltration levels and diverse immune marker sets are correlated with levels of CPZ expression in STAD. Bioinformatics analysis revealed that CPZ was involved in regulating multiple pathways, including PI3K-Akt signaling pathway, cGMP-PKG signaling pathway, Rap1 signaling pathway, TGF-beta signaling pathway, regulation of cell adhesion, extracellular matrix organization, collagen fibril organization, collagen catabolic process. Conclusion: This study for the first time provides useful information to understand the potential roles of CPZ in tumor immunology and validate it to be a potential biomarker for GC.

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The m6A methyltransferase METTL14 inhibits the proliferation, migration, and invasion of gastric cancer by regulating the PI3K/AKT/mTOR signaling pathway

Journal of Clinical Laboratory Analysis ◽

10.1002/jcla.23655 ◽

2020 ◽

Author(s):

Xin Liu ◽

Mingyang Xiao ◽

Liang Zhang ◽

Liuli Li ◽

Guolian Zhu ◽

...

Keyword(s):

Gastric Cancer ◽

Signaling Pathway ◽

Mtor Signaling ◽

Migration And Invasion ◽

Mtor Signaling Pathway

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Interrogation of gender disparity uncovers androgen receptor as the transcriptional activator for oncogenic miR-125b in gastric cancer

Cell Death and Disease ◽

10.1038/s41419-021-03727-3 ◽

2021 ◽

Vol 12 (5) ◽

Author(s):

Ben Liu ◽

Meng Zhou ◽

Xiangchun Li ◽

Xining Zhang ◽

Qinghua Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Androgen Receptor ◽

Signaling Pathway ◽

Gender Bias ◽

Gender Disparity ◽

Gene Set Enrichment Analysis ◽

Cancer Type ◽

Female Patients

AbstractThere is a male preponderance in gastric cancer (GC), which suggests a role of androgen and androgen receptor (AR). However, the mechanism of AR signaling in GC especially in female patients remains obscure. We sought to identify the AR signaling pathway that might be related to prognosis and examine the potential clinical utility of the AR antagonist for treatment. Deep learning and gene set enrichment analysis was used to identify potential critical factors associated with gender bias in GC (n = 1390). Gene expression profile analysis was performed to screen differentially expressed genes associated with AR expression in the Tianjin discovery set (n = 90) and TCGA validation set (n = 341). Predictors of survival were identified via lasso regression analyses and validated in the expanded Tianjin cohort (n = 373). In vitro and in vivo experiments were established to determine the drug effect. The GC gender bias was attributable to sex chromosome abnormalities and AR signaling dysregulation. The candidates for AR-related gene sets were screened, and AR combined with miR-125b was associated with poor prognosis, particularly among female patients. AR was confirmed to directly regulate miR-125b expression. AR-miR-125b signaling pathway inhibited apoptosis and promoted proliferation. AR antagonist, bicalutamide, exerted anti-tumor activities and induced apoptosis both in vitro and in vivo, using GC cell lines and female patient-derived xenograft (PDX) model. We have shed light on gender differences by revealing a hormone-regulated oncogenic signaling pathway in GC. Our preclinical studies suggest that AR is a potential therapeutic target for this deadly cancer type, especially in female patients.

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