Galectin-8 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

of the

galectin Galectins are a class of proteins that bind specifically to β-galactoside sugars, such as ''N''-acetyllactosamine (Galβ1-3GlcNAc or Galβ1-4GlcNAc), which can be bound to proteins by either N-linked or O-linked glycosylation. They are also te ...

family that in humans is encoded by the ''LGALS8''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

Function

This gene encodes a member of the galectin family. Galectins are beta-galactoside-binding animal

lectin Lectins are carbohydrate-binding proteins that are highly specific for sugar Moiety (chemistry), groups that are part of other molecules, so cause agglutination (biology), agglutination of particular cells or precipitation of glycoconjugates an ...

s with conserved carbohydrate recognition domains. The galectins have been implicated in many essential functions including development, differentiation, cell-cell

adhesion Adhesion is the tendency of dissimilar particles or interface (matter), surfaces to cling to one another. (Cohesion (chemistry), Cohesion refers to the tendency of similar or identical particles and surfaces to cling to one another.) The ...

, cell-

matrix Matrix (: matrices or matrixes) or MATRIX may refer to: Science and mathematics * Matrix (mathematics), a rectangular array of numbers, symbols or expressions * Matrix (logic), part of a formula in prenex normal form * Matrix (biology), the m ...

interaction, growth regulation,

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

, and

RNA splicing RNA splicing is a process in molecular biology where a newly-made precursor messenger RNA (pre-mRNA) transcription (biology), transcript is transformed into a mature messenger RNA (Messenger RNA, mRNA). It works by removing all the introns (non-cod ...

. This gene is widely expressed in tumoral tissues and seems to be involved in

integrin Integrins are transmembrane receptors that help cell–cell and cell–extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, o ...

-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. Galectin-8 controls

mTOR The mammalian target of rapamycin (mTOR), also referred to as the mechanistic target of rapamycin, and sometimes called FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the ''MTOR'' gene. ...

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 Autophagy (or autophagocytosis; from the Greek language, Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-depe ...

and

metabolic Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the ...

switching.

Galectin-8 levels

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.

Role in cancer

Galectin-8 has a complex role in cancer, sometimes being protumorigenic and other times anti-tumorigenic.

Role in cellular defence

Galectin-8 has recently been shown to have a role in cellular defence, against both bacterial cytosolic infection and vacuolar damage. 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

adaptors such as NDP52 leading to the formation of an

autophagosome An autophagosome is a spherical structure with double layer membranes. It is the key structure in macroautophagy, the intracellular degradation system for cytoplasmic contents (e.g., abnormal intracellular proteins, excess or damaged organelles, i ...

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.

Engineered galectin-8 assays

Galectin-8 has also been used to study endosomal disruption in the development of nanoscale

drug delivery systems In pharmacology and toxicology, a route of administration is the way by which a drug, fluid, poison, or other substance is taken into the body. Routes of administration are generally classified by the location at which the substance is applied. ...

. Many drug delivery systems carrying large molecule drugs, such as antisense oligonucleotides,

siRNA Small interfering RNA (siRNA), sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded non-coding RNA molecules, typically 20–24 base pairs in length, similar to microRNA (miRNA), and operating within the RN ...

peptides Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Dalton (unit), Da or more are called proteins. Chains of fewer t ...

, and

therapeutic proteins A therapy or medical treatment is the attempted remediation of a health problem, usually following a medical diagnosis. Both words, ''treatment'' and ''therapy'', are often abbreviated tx, Tx, or Tx. As a rule, each therapy has indications an ...

, 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.

Interactions

Galectin-8 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...

with

CD44 The CD44 antigen is a cell-surface glycoprotein involved in cell–cell interactions, cell adhesion and migration. In humans, the CD44 antigen is encoded by the ''CD44'' gene on chromosome 11. CD44 has been referred to as HCAM (homing cell adhes ...

CD49d CD49d is an integrin Integrins are transmembrane receptors that help cell–cell and cell–extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulat ...

CD29 Integrin beta-1 (ITGB1), also known as CD29, is a cell surface receptor that in humans is encoded by the ''ITGB1'' gene. This integrin associates with integrin alpha 1 and integrin alpha 2 to form integrin complexes which function as collagen ...

and

CD49c Integrin alpha-3 is a protein that in humans is encoded by the ''ITGA3'' gene. ITGA3 is an integrin alpha subunit. Together with beta-1 subunit, it makes up half of the α3β1 integrin duplex that plays a role in neural migration and corticogene ...

. It also interacts with components of the

mTORC1 mTORC1, also known as mammalian target of rapamycin complex 1 or mechanistic target of rapamycin complex 1, is a protein complex that functions as a nutrient/energy/redox sensor and controls protein synthesis. mTOR Complex 1 (mTORC1) is comp ...

complex.