IGSF8 explained

Immunoglobulin superfamily member 8 is a protein that in humans is encoded by the IGSF8 gene.^{[1] [2] [3]} IGSF8 has also been designated as CD316 (cluster of differentiation 316). IGSF8 is an innate immune checkpoint that inhibits the cytotoxic activity of natural killer (NK) cells.^[4] IGSF8 acts by binding to the Killer Ig-like Receptor KIR3DL2 (or, in mice, the analogous Klra9 receptor). IGSF8 is frequently overexpressed relative to normal tissues in many cancers, included melanoma, urothelial carcinoma, and breast cancer, and has been proposed as a potential therapeutic target in gliomas.^[5] In normal tissues, IGSF8 is highly expressed in the brain, where it may contribute to the immune privilege of the central nervous system.

IGSF8 as a Cancer Biomarker

In gliomas, IGSF8 is strongly correlated with tumor grade and is a potential prognostic marker. IGSF8 is enriched on ovarian cancer-derived extracellular vesicles and is a potential biomarker for the early detection of high grade serous ovarian cancer.^[6]

Further reading

• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Charrin S, Le Naour F, Labas V, etal . EWI-2 is a new component of the tetraspanin web in hepatocytes and lymphoid cells. . Biochem. J. . 373 . Pt 2 . 409–21 . 2003 . 12708969 . 10.1042/BJ20030343 . 1223506 .
• Zhang XA, Lane WS, Charrin S, etal . EWI2/PGRL associates with the metastasis suppressor KAI1/CD82 and inhibits the migration of prostate cancer cells. . Cancer Res. . 63 . 10 . 2665–74 . 2003 . 12750295 .
• Bonkobara M, Das A, Takao J, etal . Identification of novel genes for secreted and membrane-anchored proteins in human keratinocytes. . Br. J. Dermatol. . 148 . 4 . 654–64 . 2003 . 12752121 . 10.1046/j.1365-2133.2003.05244.x . 21635573 .
• Stipp CS, Kolesnikova TV, Hemler ME . EWI-2 regulates alpha3beta1 integrin-dependent cell functions on laminin-5. . J. Cell Biol. . 163 . 5 . 1167–77 . 2004 . 14662754 . 10.1083/jcb.200309113 . 2173626 .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Kolesnikova TV, Stipp CS, Rao RM, etal . EWI-2 modulates lymphocyte integrin alpha4beta1 functions. . Blood . 103 . 8 . 3013–9 . 2004 . 15070678 . 10.1182/blood-2003-07-2201 . free .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Yang XH, Kovalenko OV, Kolesnikova TV, etal . Contrasting effects of EWI proteins, integrins, and protein palmitoylation on cell surface CD9 organization. . J. Biol. Chem. . 281 . 18 . 12976–85 . 2006 . 16537545 . 10.1074/jbc.M510617200 . free .
• Sala-Valdés M, Ursa A, Charrin S, etal . EWI-2 and EWI-F link the tetraspanin web to the actin cytoskeleton through their direct association with ezrin-radixin-moesin proteins. . J. Biol. Chem. . 281 . 28 . 19665–75 . 2006 . 16690612 . 10.1074/jbc.M602116200 . free .
• Kettner S, Kalthoff F, Graf P, etal . EWI-2/CD316 is an inducible receptor of HSPA8 on human dendritic cells. . Mol. Cell. Biol. . 27 . 21 . 7718–26 . 2007 . 17785435 . 10.1128/MCB.00180-07 . 2169036 .

Notes and References

1. Stipp CS, Kolesnikova TV, Hemler ME . EWI-2 is a major CD9 and CD81 partner and member of a novel Ig protein subfamily . J Biol Chem . 276 . 44 . 40545–54 . Oct 2001 . 11504738 . 10.1074/jbc.M107338200 . free .
2. Clark KL, Zeng Z, Langford AL, Bowen SM, Todd SC . PGRL is a major CD81-associated protein on lymphocytes and distinguishes a new family of cell surface proteins . J Immunol . 167 . 9 . 5115–21 . Oct 2001 . 11673522 . 10.4049/jimmunol.167.9.5115. free .
3. Web site: Entrez Gene: IGSF8 immunoglobulin superfamily, member 8.
4. Li . Yulong . Wu . Xiangyang . Sheng . Caibin . Liu . Hailing . Liu . Huizhu . Tang . Yixuan . Liu . Chao . Ding . Qingyang . Xie . Bin . Xiao . Xi . Zheng . Rongbin . Yu . Quan . Guo . Zengdan . Ma . Jian . Wang . Jin . May 2024 . IGSF8 is an innate immune checkpoint and cancer immunotherapy target . Cell . 187 . 11 . 2703–2716.e23 . 10.1016/j.cell.2024.03.039 . 38657602 . 0092-8674.
5. Ren . Jiaxing . Huang . Ping . Wang . Fei . September 2024 . IGSF8 is a potential target for the treatment of gliomas . Asian Journal of Surgery . en . 47 . 9 . 3883–3891 . 10.1016/j.asjsur.2024.02.118. free .
6. Trinidad . Camille V. . Pathak . Harsh B. . Cheng . Shibo . Tzeng . Shin-Cheng . Madan . Rashna . Sardiu . Mihaela E. . Bantis . Leonidas E. . Deighan . Clayton . Jewell . Andrea . Rayamajhi . Sagar . Zeng . Yong . Godwin . Andrew K. . 2023-10-26 . Lineage specific extracellular vesicle-associated protein biomarkers for the early detection of high grade serous ovarian cancer . Scientific Reports . en . 13 . 1 . 18341 . 10.1038/s41598-023-44050-5 . 2045-2322 . 10603107 . 37884576. 2023NatSR..1318341T .