Galectin-8

This gene encodes a member of the galectin family. Galectins are beta-galactoside-binding animal lectins with conserved carbohydrate recognition domains. The galectins have been implicated in many essential functions including development, differentiation, cell-cell adhesion, cell-matrix interaction, growth regulation, apoptosis, and RNA splicing. This gene is widely expressed in tumoral tissues and seems to be involved in integrin-like cell interactions. Alternatively spliced transcript variants encoding different isoforms have been identified.

Galectin-8, interacts with the mTOR regulatory system composed of SLC38A9, Ragulator, RagAB, RagCD.{{cite journal | vauthors = Jia J, Abudu YP, Claude-Taupin A, Gu Y, Kumar S, Choi SW, Peters R, Mudd MH, Allers L, Salemi M, Phinney B, Johansen T, Deretic V | display-authors = 6 | title = Galectins Control mTOR in Response to Endomembrane Damage | journal = Molecular Cell | volume = 70 | issue = 1 | pages = 120–135.e8 | date = April 2018 | pmid = 29625033 | pmc = 5911935 | doi = 10.1016/j.molcel.2018.03.009 }} Galectin-8 controls mTOR causing its inactivation and dissociation from damaged lysosomes, hence transducing the breach of the lysosomal membrane to mTOR. The physiological consequences of mTOR inhibition following lysosomal membrane damage encompass autophagy and metabolic switching.

Circulating galectin levels in the serum of healthy individuals typically range between 0.1 and 166.3 ng/mL, with a median concentration of approximately 6 ng/mL. In cancer patients, these levels can increase up to fivefold. {{cite journal | vauthors = Barrow H, Guo X, Wandall HH, Pedersen JW, Fu B, Zhao Q, Chen C, Rhodes JM, Yu LG | display-authors = 6 | title = Serum galectin-2, -4, and -8 are greatly increased in colon and breast cancer patients and promote cancer cell adhesion to blood vascular endothelium | journal = Clinical Cancer Research | volume = 17 | issue = 22 | pages = 7035–7046 | date = November 2011 | pmid = 21933892 | doi = 10.1158/1078-0432.CCR-11-1462 }} {{cite journal | vauthors = Tazhitdinova R, Timoshenko AV | title = The Emerging Role of Galectins and O-GlcNAc Homeostasis in Processes of Cellular Differentiation | journal = Cells | volume = 9 | issue = 8 | page = 1792 | date = July 2020 | pmid = 32731422 | pmc = 7465113 | doi = 10.3390/cells9081792 | doi-access = free }}

Galectin-8 has a complex role in cancer, sometimes being protumorigenic and other times anti-tumorigenic. {{cite journal | vauthors = Souchak J, Mohammed NB, Lau LS, Dimitroff CJ | title = The role of galectins in mediating the adhesion of circulating cells to vascular endothelium | journal = Frontiers in Immunology | volume = 15 | pages = 1395714 | date = 2024 | pmid = 38840921 | doi = 10.3389/fimmu.2024.1395714 | doi-access = free | pmc = 11150550 }}

Galectin-8 has recently been shown to have a role in cellular defence, against both bacterial cytosolic infection and vacuolar damage.{{cite journal | vauthors = Thurston TL, Wandel MP, von Muhlinen N, Foeglein A, Randow F | title = Galectin 8 targets damaged vesicles for autophagy to defend cells against bacterial invasion | journal = Nature | volume = 482 | issue = 7385 | pages = 414–8 | date = January 2012 | pmid = 22246324 | pmc = 3343631 | doi = 10.1038/nature10744 | bibcode = 2012Natur.482..414T }} Many intracellular bacteria, such as S. enterica serovar Typhimurium and S. flexneri prefer to replicate inside and outside of the vacuole safety respectively, yet these vacuoles may become damaged, exposing bacteria to the host cell cytoplasm. It has been shown that the binding of galectin-8 to the damaged vacuole can recruit autophagy adaptors such as NDP52 leading to the formation of an autophagosome and subsequent bacterial destruction. As knockout experiments of galectin-8 leads to more successful cytosolic replication by S. enterica serovar Typhimurium, it is thought that galectin-8 acts as a danger receptor in defence against intracellular pathogens.{{cite journal | vauthors = Huang J, Brumell JH | title = Microbiology: A sweet way of sensing danger | journal = Nature | volume = 482 | issue = 7385 | pages = 316–7 | date = February 2012 | pmid = 22337047 | doi = 10.1038/482316a | bibcode = 2012Natur.482..316H | s2cid = 33971618 | doi-access = free }}

Galectin-8 has also been used to study endosomal disruption in the development of nanoscale drug delivery systems. Many drug delivery systems carrying large molecule drugs, such as antisense oligonucleotides, siRNA, peptides, and therapeutic proteins, are engineered to be pH-responsive, and disrupt the endosomal membrane because of the lower pH found within progressively acidifying endosomes. Galectin-8 can be tagged with a fluorophore to track these disrupted endosomal membranes, especially when coupled with automated microscopy.{{cite journal | vauthors = Kilchrist KV, Dimobi SC, Jackson MA, Evans BC, Werfel TA, Dailing EA, Bedingfield SK, Kelly IB, Duvall CL | display-authors = 6 | title = Gal8 Visualization of Endosome Disruption Predicts Carrier-Mediated Biologic Drug Intracellular Bioavailability | journal = ACS Nano | volume = 13 | issue = 2 | pages = 1136–1152 | date = February 2019 | pmid = 30629431 | doi = 10.1021/acsnano.8b05482 | pmc = 6995262 }}

Galectin-8 has been shown to interact with CD44,{{cite journal | vauthors = Chakraborty A, Perez M, Carroll JD, Antonopoulos A, Dell A, Ortega L, Mohammed NB, Wells M, Staudinger C, Griswold A, Chandler KB, Marrero C, Jimenez R, Tani Y, Wilmott JS, Thompson JF, Wang W, Sackstein R, Scolyer RA, Murphy GF, Haslam SM, Dimitroff CJ | display-authors = 6 | title = Hypoxia Controls the Glycome Signature and Galectin-8-Ligand Axis to Promote Protumorigenic Properties of Metastatic Melanoma | journal = The Journal of Investigative Dermatology | volume = 143 | issue = 3 | pages = 456–469.e8 | date = March 2023 | pmid = 36174713 | pmc = 10123958 | doi = 10.1016/j.jid.2022.07.033 }} CD49d,{{cite journal | vauthors = Hadari YR, Arbel-Goren R, Levy Y, Amsterdam A, Alon R, Zakut R, Zick Y | title = Galectin-8 binding to integrins inhibits cell adhesion and induces apoptosis | journal = Journal of Cell Science | volume = 113 | issue = Pt 13 | pages = 2385–2397 | date = July 2000 | pmid = 10852818 | doi = 10.1242/jcs.113.13.2385 }} CD29 and CD49c. It also interacts with components of the mTORC1 complex.

{{reflist|32em}}

{{refbegin|32em}}

• {{cite journal | vauthors = Bidon N, Brichory F, Bourguet P, Le Pennec JP, Dazord L | title = Galectin-8: a complex sub-family of galectins (Review) | journal = International Journal of Molecular Medicine | volume = 8 | issue = 3 | pages = 245–50 | date = September 2001 | pmid = 11494049 | doi = 10.3892/ijmm.8.3.245 }}
• {{cite journal | vauthors = Danguy A, Camby I, Kiss R | title = Galectins and cancer | journal = Biochimica et Biophysica Acta (BBA) - General Subjects | volume = 1572 | issue = 2–3 | pages = 285–93 | date = September 2002 | pmid = 12223276 | doi = 10.1016/S0304-4165(02)00315-X }}
• {{cite journal | vauthors = Bidon-Wagner N, Le Pennec JP | title = Human galectin-8 isoforms and cancer | journal = Glycoconjugate Journal | volume = 19 | issue = 7–9 | pages = 557–63 | year = 2004 | pmid = 14758080 | doi = 10.1023/B:GLYC.0000014086.38343.98 | s2cid = 1330672 }}
• {{cite journal | vauthors = Bassen R, Brichory F, Caulet-Maugendre S, Bidon N, Delaval P, Desrues B, Dazord L | title = Expression of Po66-CBP, a type-8 galectin, in different healthy, tumoral and peritumoral tissues | journal = Anticancer Research | volume = 19 | issue = 6B | pages = 5429–33 | year = 2000 | pmid = 10697573 }}
• {{cite journal | vauthors = Hadari YR, Arbel-Goren R, Levy Y, Amsterdam A, Alon R, Zakut R, Zick Y | title = Galectin-8 binding to integrins inhibits cell adhesion and induces apoptosis | journal = Journal of Cell Science | volume = 113 ( Pt 13) | issue = 13 | pages = 2385–97 | date = July 2000 | doi = 10.1242/jcs.113.13.2385 | pmid = 10852818 }}
• {{cite journal | vauthors = Gopalkrishnan RV, Roberts T, Tuli S, Kang D, Christiansen KA, Fisher PB | title = Molecular characterization of prostate carcinoma tumor antigen-1, PCTA-1, a human galectin-8 related gene | journal = Oncogene | volume = 19 | issue = 38 | pages = 4405–16 | date = September 2000 | pmid = 10980616 | doi = 10.1038/sj.onc.1203767 | doi-access = free }}
• {{cite journal | vauthors = Bidon N, Brichory F, Hanash S, Bourguet P, Dazord L, Le Pennec JP | title = Two messenger RNAs and five isoforms for Po66-CBP, a galectin-8 homolog in a human lung carcinoma cell line | journal = Gene | volume = 274 | issue = 1–2 | pages = 253–62 | date = August 2001 | pmid = 11675018 | doi = 10.1016/S0378-1119(01)00598-4 }}
• {{cite journal | vauthors = Nagy N, Bronckart Y, Camby I, Legendre H, Lahm H, Kaltner H, Hadari Y, Van Ham P, Yeaton P, Pector JC, Zick Y, Salmon I, Danguy A, Kiss R, Gabius HJ | display-authors = 6 | title = Galectin-8 expression decreases in cancer compared with normal and dysplastic human colon tissue and acts significantly on human colon cancer cell migration as a suppressor | journal = Gut | volume = 50 | issue = 3 | pages = 392–401 | date = March 2002 | pmid = 11839721 | pmc = 1773143 | doi = 10.1136/gut.50.3.392 }}
• {{cite journal | vauthors = Maier C, Rösch K, Herkommer K, Bochum S, Cancel-Tassin G, Cussenot O, Häussler J, Assum G, Vogel W, Paiss T | display-authors = 6 | title = A candidate gene approach within the susceptibility region PCaP on 1q42.2-43 excludes deleterious mutations of the PCTA-1 gene to be responsible for hereditary prostate cancer | journal = European Urology | volume = 42 | issue = 3 | pages = 301–7 | date = September 2002 | pmid = 12234517 | doi = 10.1016/S0302-2838(02)00280-4 }}
• {{cite journal | vauthors = Ideo H, Seko A, Ishizuka I, Yamashita K | title = The N-terminal carbohydrate recognition domain of galectin-8 recognizes specific glycosphingolipids with high affinity | journal = Glycobiology | volume = 13 | issue = 10 | pages = 713–23 | date = October 2003 | pmid = 12851289 | doi = 10.1093/glycob/cwg094 | doi-access = free }}
• {{cite journal | vauthors = Nishi N, Shoji H, Seki M, Itoh A, Miyanaka H, Yuube K, Hirashima M, Nakamura T | display-authors = 6 | title = Galectin-8 modulates neutrophil function via interaction with integrin alphaM | journal = Glycobiology | volume = 13 | issue = 11 | pages = 755–63 | date = November 2003 | pmid = 12881409 | doi = 10.1093/glycob/cwg102 | doi-access = free }}

{{refend}}