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// Workers AI · dad joke modeWhat did GM3 say to GM4? You're a byte ahead.

From Wikipedia, the free encyclopedia
Structures of GM1, GM2, GM3 gangliosides

GM3 (monosialodihexosylganglioside) is a type of ganglioside. The letter G refers to ganglioside, and M is for monosialic acid as it has only one sialic acid group. The numbering is based on its relative mobility in electrophoresis among other monosialic gangliosides.[1] Its structure can be condensed to Neu5Ac-Gal-Glc-ceramide. GM3 is the most common membrane-bound glycosphingolipid in tissues, composed of three monosaccharide groups attached to a ceramide backbone.[2] GM3 serves as a precursor for other, more complex gangliosides. Like other gangliosides, GM3 is synthesized in the Golgi apparatus. It is then transported to the plasma membrane, where it functions in cellular signaling.[2] GM3 also functions as an inhibitor; it inhibits cell growth, the function of growth factor receptors, and generation of cytokines by T cells.[3]

Applications in cancer treatment

[edit]

The immunologic function of GM3 in inhibiting proliferation has resulted in its usage in the study of cancer biology and cancer treatments. GM3 has been found to reduce the motility of ovarian cancer cells, colorectal cancer cells, and gastric cancer cells. High amounts of GM3 also displayed a high amount of caveolin-1, a molecule which has been shown to inhibit ovarian cancer growth.[4] In bladder cancer cells, GM3 show antiproliferative effects. Increased concentrations of GM3 in bladder cancer cells reduces the malignancy potential of those cells and induces apoptosis.[5] The addition of GM3 to bladder cancer cells also decreases their cell adhesion and inhibits tumor growth.[6] Due to its role in inhibiting cancer growth, GM3 is a target of cancer treatments. The chemotherapy drug cisplatin functions by inducing GM3-mediated apoptosis of cancer cells.[5]

An N-glycolyl variant of GM3, Neu5Gc-GM3, in which the single sialic acid Neu5Ac has been either replaced or hydroxylated to its derivative Neu5Gc, has been found in large variety of solid tumors in humans and is strongly associated with tumor grade.[7][8] The enzyme which canonically hydroxylates Neu5Ac to Neu5Gc in vertebrates is CMAH. In humans, this enzyme exhibits a 92-bp frame-shifting deletion in a critical enzymatic binding pocket, resulting from a human-specific Alu element insertion roughly 2.5 to 3 million years ago, a process well-documented in primates and known as retrotransposition-mediated deletion.[9] As a result, modern humans exhibit no traces of Neu5Gc in any healthy tissues, and are known to exhibit circulating antibodies against Neu5Gc-containing glycans and glycoconjugates, the specific affinities of which vary among individuals.[10] To date, there is no known pathway by which Neu5Gc can be endogenously synthesized in human tissues, and thus the presence of Neu5Gc-GM3 in human cancers presents both a mystery and a promising target antigen for cancer immunotherapy.[8][11][12]

References

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  1. ↑ Puri D (2011). Biochemistry. Elseviar. ISBN 978-81-312-2312-3.
  2. 1 2 Chan RB, Perotte AJ, Zhou B, Liong C, Shorr EJ, Marder KS, et al. (2017-02-17). "Elevated GM3 plasma concentration in idiopathic Parkinson's disease: A lipidomic analysis". PLOS ONE. 12 (2) e0172348. Bibcode:2017PLoSO..1272348C. doi:10.1371/journal.pone.0172348. PMC 5315374. PMID 28212433.
  3. ↑ Tsukuda Y, Iwasaki N, Seito N, Kanayama M, Fujitani N, Shinohara Y, Kasahara Y, Onodera T, Suzuki K, Asano T, Minami A, Yamashita T (2012-06-29). Rojas M (ed.). "Ganglioside GM3 has an essential role in the pathogenesis and progression of rheumatoid arthritis". PLOS ONE. 7 (6) e40136. Bibcode:2012PLoSO...740136T. doi:10.1371/journal.pone.0040136. PMC 3387008. PMID 22768242.
  4. ↑ Hakomori SI (May 2010). "Glycosynaptic microdomains controlling tumor cell phenotype through alteration of cell growth, adhesion, and motility". FEBS Letters. 584 (9): 1901–6. Bibcode:2010FEBSL.584.1901H. doi:10.1016/j.febslet.2009.10.065. PMC 2867360. PMID 19874824.
  5. 1 2 Chung TW, Choi HJ, Kim SJ, Kwak CH, Song KH, Jin UH, Chang YC, Chang HW, Lee YC, Ha KT, Kim CH (2014-05-14). "The ganglioside GM3 is associated with cisplatin-induced apoptosis in human colon cancer cells". PLOS ONE. 9 (5) e92786. Bibcode:2014PLoSO...992786C. doi:10.1371/journal.pone.0092786. PMC 4020741. PMID 24829158.
  6. ↑ Wang H, Isaji T, Satoh M, Li D, Arai Y, Gu J (January 2013). "Antitumor effects of exogenous ganglioside GM3 on bladder cancer in an orthotopic cancer model". Urology. 81 (1): 210.e11–5. doi:10.1016/j.urology.2012.08.015. PMID 23102779.
  7. ↑ Scursoni, Alejandra M.; Galluzzo, Laura; Camarero, Sandra; Lopez, Jessica; Lubieniecki, Fabiana; Sampor, Claudia; Segatori, Valeria I.; Gabri, Mariano R.; Alonso, Daniel F.; Chantada, Guillermo; de Dávila, María Teresa G. (2011). "Detection of N-glycolyl GM3 ganglioside in neuroectodermal tumors by immunohistochemistry: an attractive vaccine target for aggressive pediatric cancer". Clinical & Developmental Immunology. 2011 245181. doi:10.1155/2011/245181. ISSN 1740-2530. PMC 3177098. PMID 21941577.
  8. 1 2 Pilco-Janeta, Daniel; De la Cruz Puebla, Myriam; Soriano, Jorge; Osorio, Marta; Caballero, Iraida; Pérez, Adanays Calvo; Savon, Laynes; Cremades, Natalia; Blanco, Rancés; Carr, Adriana (2019-06-10). "Aberrant expression of N-glycolyl GM3 ganglioside is associated with the aggressive biological behavior of human sarcomas". BMC Cancer. 19 (1): 556. doi:10.1186/s12885-019-5743-9. ISSN 1471-2407. PMC 6558727. PMID 31182063.
  9. ↑ Callinan, Pauline A.; Wang, Jianxin; Herke, Scott W.; Garber, Randall K.; Liang, Ping; Batzer, Mark A. (May 2005). "Alu Retrotransposition-mediated Deletion". Journal of Molecular Biology. 348 (4): 791–800. doi:10.1016/j.jmb.2005.02.043. ISSN 0022-2836. PMID 15843013. Archived from the original on 2024-04-12.
  10. ↑ Chou, Hsun-Hua; Hayakawa, Toshiyuki; Diaz, Sandra; Krings, Matthias; Indriati, Etty; Leakey, Meave; Paabo, Svante; Satta, Yoko; Takahata, Naoyuki; Varki, Ajit (2002-09-03). "Inactivation of CMP-N-acetylneuraminic acid hydroxylase occurred prior to brain expansion during human evolution". Proceedings of the National Academy of Sciences. 99 (18): 11736–11741. Bibcode:2002PNAS...9911736C. doi:10.1073/pnas.182257399. PMC 129338. PMID 12192086.
  11. ↑ Scursoni, Alejandra M.; Galluzzo, Laura; Camarero, Sandra; Lopez, Jessica; Lubieniecki, Fabiana; Sampor, Claudia; Segatori, Valeria I.; Gabri, Mariano R.; Alonso, Daniel F.; Chantada, Guillermo; de Dávila, María Teresa G. (2011). "Detection of N-glycolyl GM3 ganglioside in neuroectodermal tumors by immunohistochemistry: an attractive vaccine target for aggressive pediatric cancer". Clinical & Developmental Immunology. 2011 245181. doi:10.1155/2011/245181. ISSN 1740-2530. PMC 3177098. PMID 21941577.
  12. ↑ Labrada, Mayrel; Dorvignit, Denise; Hevia, Giselle; Rodríguez-Zhurbenko, Nely; Hernández, Ana M.; Vázquez, Ana M.; Fernández, Luis E. (January 2018). "GM3(Neu5Gc) ganglioside: an evolution fixed neoantigen for cancer immunotherapy". Seminars in Oncology. 45 (1–2): 41–51. doi:10.1053/j.seminoncol.2018.04.003. ISSN 1532-8708. PMID 30318083.
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