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].