FPR2 promotes invasion and metastasis of gastric cancer cells and predicts the prognosis of patients

Hou, Xi-Lu; Ji, Chao; Tang, Jun; Wang, Yanxia; Xiang, Dongfang; Li, Haiqing; Liu, Weiwei; Wang, Jiaoxue; Huang, Yan; Wang, Yan; Zhang, Peng; Cui, You‐Hong; Wang, Jiming; Bian, Xiu‐Wu; Liu, Wei

doi:10.1038/s41598-017-03368-7

Cited by 39 publications

(39 citation statements)

References 38 publications

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“…These observations suggest that FPR2 is essential for the progression of EMT during placental development. A recent study has reported that the levels of FPR2 expression is directly correlated increased proliferation and invasion during gastric cancer (GC) progression and with the patients' overall survival [15]. Using in vitro model systems, the functional role of FPR2 was linked with the regulation of invasion and metastasis of GC cells via MAPK/ERK signaling pathways and in the direct regulation of EMT.…”

Section: Discussionmentioning

confidence: 99%

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Decreased Placental FPR2 in Early Pregnancies That Later Developed Small-For-Gestation Age: A Potential Role of FPR2 in the Regulation of Epithelial-Mesenchymal Transition

Murthi

Rajaraman

Erwich

et al. 2020

Cells

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We reported earlier that an anti-inflammatory small peptide receptor-formyl peptide receptor-2 (FPR2) was significantly decreased in placentas from third trimester pregnancies complicated with fetal growth restriction (FGR), compared to placentas from uncomplicated control pregnancies, suggesting FPR2 may play a role in the development of FGR. The aim of this study is to investigate whether the actions of FPR2 alters placental growth process in humans. Accordingly, using small-for-gestation age (SGA) as a proxy for FGR, we hypothesize that FPR2 expression is decreased in first-trimester placentas of women who later manifest FGR, and contributes to aberrant trophoblast function and the development of FGR. Chorionic villus sampling (CVS) tissues were collected at 10–12 weeks gestation in 70 patients with singleton fetuses; surplus tissue was used. Real-time PCR and immunoassays were performed to quantitate FPR2 gene and protein expression. Silencing of FPR2 was performed in two independent, trophoblast-derived cell lines, HTR-8/SVneo and JEG-3 to investigate the functional consequences of FPR2 gene downregulation. FPR2 mRNA relative to 18S rRNA was significantly decreased in placentae from SGA-pregnancies (n = 28) compared with controls (n = 52) (p < 0.0001). Placental FPR2 protein was significantly decreased in SGA compared with control (n = 10 in each group, p < 0.05). Proliferative, migratory and invasive potential of the human placental-derived cell lines, HTR-8/SVneo and JEG-3 were significantly reduced in siFPR2 treated cells compared with siCONT control groups. Down-stream signaling molecules, STAT5B and SOCS3 were identified as target genes of FPR2 action in the trophoblast-derived cell lines and in SGA and control chorionic villous tissues. FPR2 is a novel regulator of key molecular pathways and functions in placental development, and its decreased expression in women destined to develop FGR reinforces a placental origin of SGA/FGR, and that it contributes to causing the development of SGA/FGR.

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Section: Discussionmentioning

confidence: 99%

“…A recent study describes that FPR2 plays an essential role in the regulation of epithelial mesenchymal transition (EMT) in tumor progression [15]. However, the potential role of FPR2 in EMT associated with early placentation is largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Decreased Placental FPR2 in Early Pregnancies That Later Developed Small-For-Gestation Age: A Potential Role of FPR2 in the Regulation of Epithelial-Mesenchymal Transition

Murthi

Rajaraman

Erwich

et al. 2020

Cells

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“…Several studies have uncovered its roles in altering neutrophils' functions and in uencing leukocytes recruitment [25,26]. More importantly, FPR2 was demonstrated to regulate the malignant transformation of human cancer cells through affecting multiple biological processes including cancer cell proliferation, migration, and invasion [27][28][29]. Moreover, a study found FPR2 could promote antitumor host defense through protecting macrophages from M2 polarization [30].…”

Section: Discussionmentioning

confidence: 99%

Identification of key genes in head and neck squamous cell carcinoma microenvironment based on gene expression profile

Xu¹,

Jin²,

Qin³

2020

Preprint

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Abstract Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent malignancy worldwide with high incidence and mortality. Recently, it has been well established that tumor microenvironment (TME) is intimately associated with cancer progression, in which the infiltration of immune and stromal cells could be exploited as effective biomarkers for cancer diagnosis and prognosis. In this study, we aimed to investigate HNSCC microenvironment to identify significant genes involved in carcinogenesis. Methods: The ESTIMATE algorithm was applied to calculate immune scores and stromal scores based on the gene expression profiles downloaded from The Cancer Genome Atlas (TCGA) database and the correlation of these scores with clinical parameters and prognosis was further analyzed. Differential expression analysis and functional enrichment analysis were performed by R software. Results: Immune scores and stromal scores were calculated by ESTIMATE algorithm and their correlations with clinicopathological characteristics of HNSCC patients were identified. Differentially expressed genes (DEGs) based on two scores were identified and subjected to functional analysis, demonstrating their close associations with tumor immunity. Hub genes were selected from which CCR2, CCR4, CCR8 and P2RY14 were found to be significantly associated with the survival rate of HNSCC patients. Conclusions: In summary, we made a comprehensive analysis of HNSCC microenvironment and illustrated several key immune-related genes, which may provide evidences for the development of precision immunotherapy.

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“…Previous study showed that FPR2 deficiency increased secretion of CCL2 and facilitated M2 polarization of macrophages, promoting tumor progression [30]. In addition, FPR2 enhanced invasion and migration of cancer cells in gastric cancer and colorectal cancer [31,32]. Mathern et al found that T cellexpressed C3AR1 amplified the expression of antigen presenting cell costimulatory molecules and innate cytokines, promoting CD8 + T cell proliferation and expansion [33].…”

Section: Kinase Targets Of Hub Genesmentioning

confidence: 99%

Identification of genes with therapeutic and prognostic values in lung adenocarcinoma microenvironment

Jiang¹,

Gao²,

Zhang³

et al. 2020

Preprint

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Background As the most diagnosed malignancy, lung cancer is also the primary cause of cancer death in the entire world. The therapy of lung adenocarcinoma (LUAD), which is the most prevalent subtype of lung cancer, draw researchers’ increasing attentions. This research aimed to investigate the tumor microenvironment (TME)-related hub genes which might be novel targets for treatment. Materials and methods LUAD-associated data packages, including RNA-Seq information and clinical data of 522 patients, were obtained from The Cancer Genome Atlas (TCGA). For better evaluation of stromal and immune cell components, immune scores, stromal scores and estimate scores were obtained with ESTIMATE algorithm based on gene expression levels in tumors. The R package heatmap and clustering analysis were used to explore interested genes. Differentially expressed genes (DEGs) were identified by Venn diagram. Protein-protein interaction (PPI) network was applied to explore intrinsic connections of DEGs. Kaplan-Meier (K-M) survival curves, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied to investigate the prognostic values and intricate biological functions of DEGs. The relationships between 4 survival-related hub genes and 6 types of immune cells were examined using TIMER database. The LinkedOmics database was applied to look for kinase targets of hub genes. Results The immune/stromal/estimate scores were significantly correlated with clinical features, including the grades and sizes of LUAD, distant metastasis and outcomes. A total of 702 DEGs, 589 up-regulated and 113 down-regulated, were identified. GO and KEGG analysis showed that the DEGs had significant correlations with tumor immunology. PPI network suggested that the top 8 nodes were FPR2, C3AR1, MCHR1, CCR5, FPR1, CCL19, CCR2 and CXCL10. K-M survival curves indicated that FPR2, C3AR1, MCHR1 and CCR5, as hub genes, were significantly correlated with the overall survival (OS) of LUAD patients. The expression levels of C3AR1 and CCR5 were positively correlated with immune cell infiltration. LYN, LCK and SYK were the targeted kinases of these hub genes. Conclusion FPR2, C3AR1, MCHR1 and CCR5 were TME-related genes and potential biomarkers for the therapy and prognosis of LUAD.

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FPR2 promotes invasion and metastasis of gastric cancer cells and predicts the prognosis of patients

Cited by 39 publications

References 38 publications

Decreased Placental FPR2 in Early Pregnancies That Later Developed Small-For-Gestation Age: A Potential Role of FPR2 in the Regulation of Epithelial-Mesenchymal Transition

Decreased Placental FPR2 in Early Pregnancies That Later Developed Small-For-Gestation Age: A Potential Role of FPR2 in the Regulation of Epithelial-Mesenchymal Transition

Identification of key genes in head and neck squamous cell carcinoma microenvironment based on gene expression profile

Identification of genes with therapeutic and prognostic values in lung adenocarcinoma microenvironment

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