Folia Neuropathologica
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ISSN: 1641-4640
Folia Neuropathologica
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Original paper

TREM2/DAP12 complex promotes proliferation and invasion of glioma cells via the PI3K-AKT signaling pathway

Zhitong Deng
1
,
Xingming Zhong
1
,
Yong Cai
1
,
Jianguo Yang
1
,
Yiqi Wang
1
,
Zhenhai Fei
1
,
Hua Gu
1
,
Tao Yang
1
,
Zhaohui Zhao
1

  1. Department of Neurosurgery, The First People’s Hospital of Huzhou (First Affiliated Hospital of Huzhou University), Huzhou, Zhejiang 313000, China
Folia Neuropathol 2025; 63
Online publish date: 2025/11/27
Article file
- 01817 - TREM2.pdf  [6.29 MB]
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1. Ford JW, Gonzalez-Cotto M, MacFarlane AW, Peri S, Howard OMZ, Subleski JJ, Ruth KJ, Haseebuddin M, Al-Saleem T, Yang Y, Rayman P, Rini B, Marston Linehan W, Finke J, Weiss JM, Campbell KS, McVicar DW. Tumor-infiltrating myeloid cells co-express TREM1 and TREM2 and elevated TREM-1 associates with disease progression in renal cell carcinoma. Front Oncol 2021; 11: 662723.
2. Gao X, Guo X, Xue H, Qiu W, Guo X, Zhang J, Qian M, Li T, Liu Q, Shen J, Deng L, Li G. lncTCF7 is a negative prognostic factor, and knockdown of lncTCF7 inhibits migration, proliferation and tumorigenicity in glioma. Sci Rep 2017; 7: 17456.
3. Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E, Majounie E, Cruchaga C, Sassi C, Kauwe JSK, Younkin S, Hazrati L, Collinge J, Pocock J, Lashley T, Williams J, Lambert JC, Amouyel P, Goate A, Rademakers R, Morgan K, Powell J, St George-Hyslop P, Singleton A, Hardy J; Alzheimer Genetic Analysis Group. TREM2 variants in Alzheimer’s disease. N Engl J Med 2013; 368: 117-127.
4. Haure-Mirande JV, Audrain M, Ehrlich ME, Gandy S. Microglial TYROBP/DAP12 in Alzheimer’s disease: Transduction of physiological and pathological signals across TREM2. Mol Neurodegener 2022; 17: 55.
5. Kim HY, Kim DK, Bae SH, Gwak HR, Jeon JH, Kim JK, Lee BI, You HJ, Shin DH, Kim YH, Kim SY, Han SS, Shim JK, Lee JH, Kang SG, Jang H. Farnesyl diphosphate synthase is important for the maintenance of glioblastoma stemness. Exp Mol Med 2018; 50: 1-12.
6. Kim SM, Kim EM, Ji KY, Lee HY, Yee SM, Woo SM, Yi JW, Yun CH, Choi H, Kang HS. TREM2 acts as a tumor suppressor in colorectal carcinoma through Wnt1/b-catenin and Erk signaling. Cancers (Basel) 2019; 11: 1315.
7. Kluckova K, Kozak J, Szaboova K, Rychly B, Svajdler M, Suchankova M, Tibenska E, Filova B, Steno J, Matejcik V, Homolova M, Bucova M. TREM-1 and TREM-2 expression on blood monocytes could help predict survival in high-grade glioma patients. Mediators Inflamm 2020; 2020: 1798147.
8. Li C, Hou X, Yuan S, Zhang Y, Yuan W, Liu X, Li J, Wang Y, Guan Q, Zhou Y. High expression of TREM2 promotes EMT via the PI3K/AKT pathway in gastric cancer: bioinformatics analysis and experimental verification. J Cancer 2021; 12: 3277-3290.
9. Li X, Tao Z, Wang H, Deng Z, Zhou Y, Du Z. Dual inhibition of Src and PLK1 regulate stemness and induce apoptosis through Notch1-SOX2 signaling in EGFRvIII positive glioma stem cells (GSCs). Exp Cell Res 2020; 396: 112261.
10. Liu Y, Li R, Chen XX, Zhi Y, Deng R, Zhou EM, Qiao S, Zhang G. Nonmuscle myosin heavy chain IIA recognizes sialic acids on sialylated RNA viruses to suppress proinflammatory responses via the DAP12-syk pathway. mBio 2019; 10: e00574-19.
11. Park MD, Reyes-Torres I, LeBerichel J, Hamon P, LaMarche NM, Hegde S, Belabed M, Troncoso L, Grout JA, Magen A, Humblin E, Nair A, Molgora M, Hou J, Newman JH, Farkas AM, Leader AM, Dawson T, D’Souza D, Hamel S, Sanchez-Paulete AR, Maier B, Bhardwaj N, Martin JC, Kamphorst AO, Kenigsberg E, Casanova-Acebes M, Horowitz A, Brown BD, De Andrade LF, Colonna M, Marron TU, Merad M. TREM2 macrophages drive NK cell paucity and dysfunction in lung cancer. Nat Immunol 2023; 24: 792-801.
12. Shen H, Xu L, You C, Tang H, Wu H, Zhang Y, Xie M. miR-665 is downregulated in glioma and inhibits tumor cell proliferation, migration and invasion by targeting high mobility group box 1. Oncol Lett 2021; 21: 156.
13. Tang W, Lv B, Yang B, Chen Y, Yuan F, Ma L, Chen S, Zhang S, Xia J. TREM2 acts as a tumor suppressor in hepatocellular carcinoma by targeting the PI3K/Akt/b-catenin pathway. Oncogenesis 2019; 8: 9.
14. Wang HY, Yang FC, Yang CF, Liu YC, Ko PS, Li CJ, Tsai CK, Chung YL, Chen NJ. Surface TREM2 on circulating M-MDSCs as a novel prognostic factor for adults with treatment-naïve diffuse large B-cell lymphoma. Exp Hematol Oncol 2023; 12: 35.
15. Wang XQ, Tao BB, Li B, Wang XH, Zhang WC, Wan L, Hua XM, Li ST. Overexpression of TREM2 enhances glioma cell proliferation and invasion: a therapeutic target in human glioma. Oncotarget 2016; 7: 2354-2366.
16. Wang Z, Zhou H, Cheng F, Zhang Z, Long S. miR-21 negatively regulates the PTEN-PI3K-Akt-mTOR signaling pathway in Crohn’s disease by altering immune tolerance and epithelial-mesenchymal transition. Discov Med 2022; 34: 45-58.
17. Wei R, Zhang L, Hu W, Wu J, Zhang W. CSTA plays a role in osteoclast formation and bone resorption by mediating the DAP12/TREM2 pathway. Biochem Biophys Res Commun 2022; 627: 12-20.
18. Wißfeld J, Mathews M, Mossad O, Picardi P, Cinti A, Redaelli L, Pradier L, Brüstle O, Neumann H. Reporter cell assay for human CD33 validated by specific antibodies and human iPSC-derived microglia. Sci Rep 2021; 11: 13462.
19. Yao Y, Li H, Chen J, Xu W, Yang G, Bao Z, Xia D, Lu G, Hu S, Zhou J. TREM-2 serves as a negative immune regulator through Syk pathway in an IL-10 dependent manner in lung cancer. Oncotarget 2016; 7: 29620-29634.
20. Yu M, Chang Y, Zhai Y, Pang B, Wang P, Li G, Jiang T, Zeng F. TREM2 is associated with tumor immunity and implies poor prognosis in glioma. Front Immunol 2022; 13: 1089266.
21. Zarbock A, Abram CL, Hundt M, Altman A, Lowell CA, Ley K. PSGL-1 engagement by E-selectin signals through Src kinase Fgr and ITAM adapters DAP12 and FcR gamma to induce slow leukocyte rolling. J Exp Med 2008; 205: 2339-2347.
22. Zhang H, Sheng L, Tao J, Chen R, Li Y, Sun Z, Qian W. Depletion of the triggering receptor expressed on myeloid cells 2 inhibits progression of renal cell carcinoma via regulating related protein expression and PTEN-PI3K/Akt pathway. Int J Oncol 2016; 49: 2498-2506.
23. Zhong L, Chen XF, Zhang ZL, Wang Z, Shi XZ, Xu K, Zhang YW, Xu H, Bu G. DAP12 stabilizes the C-terminal fragment of the triggering receptor expressed on myeloid cells-2 (TREM2) and protects against LPS-induced pro-inflammatory response. J Biol Chem 2015; 290: 15866-15877.
Copyright: © 2025 Mossakowski Medical Research Centre Polish Academy of Sciences and the Polish Association of Neuropathologists. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
 
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