Glyphosate, FAK and Anoikis
The motif Arginine-Glycine-Aspartate (RGD), expressed in integrin
ligands, is the recognition site for integrin binding to these ligands,
and it regulates cell-cell and cell-extracellular matrix (ECM)
interactions. Short synthetic peptides that contain the RGD sequence
promote cell adhesion when adhered onto a surface, by binding to
integrins in the cell membrane, and inhibit it through a decoy
phenomenon when presented to cells in solution [137]. It has been
proposed and demonstrated experimentally that glyphosate has biomimetic
features that cause it to disrupt cellular adhesion properties in
unpredictable ways. Glyphosate can mimic an RGD binding site, and, as a
consequence, glyphosate adsorbed on the surface of a cell enhances
cellular adhesion. By contrast, glyphosate in solution can act as a
decoy to interfere with focal adhesion. These authors hypothesized that
the interference of glyphosate in solution with cellular adhesion
processes could trigger anoikis [138]. Anoikis (“homelessness” in
Greek) is a form of apoptosis that is induced by disrupted cell–ECM
interactions [139].
Inappropriate cell-substrate contact triggers anoikis [140]. FAK
gene silencing has been shown to promote anoikis in adenocarcinoma cells
[140]. This is consistent with the idea that neuronal cell death by
anoikis would be a feature of autism, given that FAK signaling is
reduced in association with autism [134]. Thus, downregulation of
FAK/SRC signaling in autism due to decreased FAK activity is expected to
lead to enhanced apoptosis by anoikis in the brains of autistic
individuals [132,141].