Ej. Meuillet et al., Modulation of EGF receptor activity by changes in the GM3 content in a human epidermoid carcinoma cell line, A431, EXP CELL RE, 256(1), 2000, pp. 74-82
Gangliosides have been described as modulators of growth factor receptors.
For example, GM3 addition in cell culture medium inhibits epidermal growth
factor (EGF)-stimulated receptor autophosphorylation. Furthermore, depletio
n of ganglioside by sialidase gene transfection appeared to increase EGF re
ceptor (EGFR) autophosphorylation. These data suggested that changes in GM3
content may result in different responses to EGF. In this study, the ceram
ide analog D-threo-1-phenyl-2-decannoylamino-3-morpholino-1-propanol ([D]-P
DMP), which inhibits UDP-glucoseceramide glucosyltransferase, and addition
of GM3 to the culture medium mere used to study the effects of GM3 on the E
GFR. Addition of 10 mu M [D]-PDMP to A431 cells resulted in significant GM3
depletion. Additionally, EGFR autophosphorylation was increased after EGF
stimulation; When exogenous GM3 was added in combination with [D]-PDMP, the
enhanced EGFR autophosphorylation was returned to control levels. [D]-PDMP
also increased EGF-induced cell proliferation, consistent with its effect
on autophosphorylation. Once again, the addition of GM3 in combination with
[D]-PDMP reversed these effects. These results indicate that growth factor
receptor functions can be modulated by the level of ganglioside expression
in cell lines. Addition of GM3 inhibits EGFR activity and decrease of GM3
levels using [D]-PDMP treatment enhances EGFR activity. Modulation of growt
h factor receptor function may provide an explanation for how transformatio
n-dependent ganglioside changes contribute to the transformed phenotype. (C
) 2000 Academic Press.