TREM2 acts as a tumor suppressor in hepatocellular carcinoma by targeting the PI3K/Akt/β-catenin pathway

Tang, Wenyi; Lv, Bei; Yang, Biwei; Chen, Yukai; Yuan, Feifei; Ma, Li; Chen, She; Zhang, Si; Xia, Jinglin

doi:10.1038/s41389-018-0115-x

Cited by 53 publications

(44 citation statements)

References 39 publications

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“…In this study, TREM2 overexpression suppressed HCC progression by regulating the PI3K/Akt/β-catenin pathway. Furthermore, reduced TREM2 expression is observed in the poor prognosis of HCC patients [122]. Another study supports the protective role of TREM2 in hepatocarcinogenesis.…”

Section: Roles Of Trem In Liver Tumorigenesismentioning

confidence: 66%

Function of TREM1 and TREM2 in Liver-Related Diseases

Sun

Feng

Tang

2020

Cells

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TREM1 and TREM2 are members of the triggering receptors expressed on myeloid cells (TREM) family. Both TREM1 and TREM2 are immunoglobulin superfamily receptors. Their main function is to identify foreign antigens and toxic substances, thereby adjusting the inflammatory response. In the liver, TREM1 and TREM2 are expressed on non-parenchymal cells, such as liver sinusoidal endothelial cells, Kupffer cells, and hepatic stellate cells, and cells which infiltrate the liver in response to injury including monocyte-derived macrophages and neutrophils. The function of TREM1 and TREM2 in inflammatory response depends on Toll-like receptor 4. TREM1 mainly augments inflammation during acute inflammation, while TREM2 mainly inhibits chronic inflammation to protect the liver from pathological changes. Chronic inflammation often induces metabolic abnormalities, fibrosis, and tumorigenesis. The above physiological changes lead to liver-related diseases, such as liver injury, nonalcoholic steatohepatitis, hepatic fibrosis, and hepatocellular carcinoma. Here, we review the function of TREM1 and TREM2 in different liver diseases based on inflammation, providing a more comprehensive perspective for the treatment of liver-related diseases.

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Section: Roles Of Trem In Liver Tumorigenesismentioning

confidence: 66%

Function of TREM1 and TREM2 in Liver-Related Diseases

Sun

Feng

Tang

2020

Cells

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“…Borromeo et al (32) reported that NEUROD1 plays crucial roles in promoting malignant behaviour and survival in patients with SCLC. TREM2, a novel pattern recognition receptor family member, is generally regarded to be an enhancer of immune responses (33). According to pharmacogenomics, NRG3 rs1649942 genetic variants have been validated to affect epithelial ovarian cancer first-line treatment outcomes, which confirmed patients carrying the NRG3 rs1649942 A allele presented a significantly longer OS time (34).…”

Section: Discussionmentioning

confidence: 98%

Time‑series clustering of cytokine expression after transarterial chemoembolization in patients with hepatocellular carcinoma

et al. 2019

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Cytokines play an important role in the development of tumors. The purpose of the present study was to evaluate the mechanisms and cytokine level changes after transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). The Short Time-series Expression Miner (STEM) program was utilized to cluster cytokine expression profiles from the day before TACE to day 21 post-TACE. Based on the identified significant signatures, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed. Cytokines were serially monitored in 60 evaluable patients to identify the results of the STEM program. Examination of the significant signatures identified 6 significant time-varied expression patterns for 507 cytokines (profiles 16, 18, 28, 41, 42 and 43). GO analysis was enriched in 'cytokine receptor-binding' and 'cytokine receptor activity', and the identified signaling pathways included 'cytokine-cytokine receptor interaction' and the 'JAK-STAT signaling pathway'. Ciliary neurotrophic factor (CNTF) level was increased early after TACE, reaching a peak on day 7 before finally decreasing from day 14 onwards, and was significantly positively correlated with aminotransferase level. Serum levels of pre-TACE IL-10 predicted the local tumor response and overall survival (OS) of the patients, while serum levels of post-TACE IL-1β only indicated the local tumor response of the patient. Overall, the present study identified cytokine time-series expression profiles of patients with HCC undergoing TACE. Early phase increases in CNTF after TACE were associated with post-treatment hepatic injury. IL-1β may reflect an objective response after TACE, while IL-10 may represent a biomarker for OS and the objective response pre-TACE, which may help patients with HCC to benefit from TACE.

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“…Knockdown of TREM-2 induced cell proliferation, migration, and increased invasive potential “ in vivo ” and “ in vitro ,” while TREM-2 overexpression had the opposite effect. TREM-2 also retarded the growth of metastases of HCC [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

TREM-1 and TREM-2 Expression on Blood Monocytes Could Help Predict Survival in High-Grade Glioma Patients

Klučková

Kozák

Szaboova

et al. 2020

Mediators of Inflammation

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Objective. In recent years, the role of the modern inflammatory markers TREM-1 (triggering receptors expressed on myeloid cells) and HMGB1 (high mobility group box 1 protein) in tumorigenesis has begun to be studied. Their role in gliomas is not clear. The aim of our study was to find the role of inflammation in gliomas. Patients and Methods. In 63 adult patients with gliomas and 31 healthy controls, the expressions of TREM-1 and TREM-2 on CD14+ blood cells (method: flow cytometry) and the levels of soluble sTREM-1, HMGB1, IL-6, and IL-10 (Elisa tests) were analyzed. Results. Cox proportional hazard analysis showed that a TREM-1/TREM-2 ratio was associated with reduced overall survival (HR=1.001, P=0.023). Patients with a TREM-1/TREM-2 ratio above 125 survived significantly shorter than patients with a TREM-1/TREM-2 ratio below 125. The percentage of CD14+ TREM-1+ cells was strongly associated with a plasma IL-6/IL-10 ratio (positively) and with IL-10 (negatively). Conversely, we found a higher percentage of CD14+ TREM-2+ monocytes in better surviving patients; these cells could downregulate the exaggerated inflammation and potentiate the phagocytosis in the tumor. The serum levels of HMGB1 negatively correlated with the percentage of CD14+ TREM-1+ cells and with the TREM-1/TREM-2 ratio. The positive correlation between the serum levels of a late proinflammatory cytokine HMGB1 with the percentage of TREM2+ CD14+ monocytes can be explained as an effort for suppression of systemic inflammation by anti-inflammatory acting CD14+ TREM-2+ cells. Conclusion. We showed that the TREM-1/TREM-2 ratio (expression on the surface of blood monocytes) could help predict prognosis in patients with gliomas, especially in high-grade gliomas, and that systemic inflammation has an impact on the patient’s overall survival. This is the first study that showed that TREM expression on monocytes in peripheral blood could help predict prognosis in patients with gliomas.

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TREM2 acts as a tumor suppressor in hepatocellular carcinoma by targeting the PI3K/Akt/β-catenin pathway

Cited by 53 publications

References 39 publications

Function of TREM1 and TREM2 in Liver-Related Diseases

Function of TREM1 and TREM2 in Liver-Related Diseases

Time‑series clustering of cytokine expression after transarterial chemoembolization in patients with hepatocellular carcinoma

TREM-1 and TREM-2 Expression on Blood Monocytes Could Help Predict Survival in High-Grade Glioma Patients

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