Modulation of gonadotrophins on breast cancer cell movement via FAK and moesin.

UZAIR ID; NEIRA FJ; FLAMINI MI; JAHN GA; SANCHEZ AM

Potrero de los Funes

Congreso; XXX Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2012

Sociedad de Biología de Cuyo

Breast cancer (BC) is the most frequent malignancy in Western countries. Most BC are hormone dependent and are affected by therapies that reduce these hormones levels or interfere with their receptors. Luteinizing hormone (LH) and follicle stimulating hormone (FSH) are synthesized and secreted by the pituitary gonadotrope in response to pulsatile GnRH (Gonadotrophin-Releasing Hormone). The effects of gonadotrophins LH and FSH are poorly investigated in BC movement. Actin remodeling and cell movement are fundamental for breast cancer function and are controlled by the actin-binding protein moesin and focal adhesion kinase FAK. We studied the extra-gonadal actions of FSH and LH on moesin and FAK activation, with a specific focus on cellular movement, more specifically, on the migration and invasion in T47-D BC cells. Our findings show that LH and FSH trigger a rapid actin rearrangement, with the formation of cortical actin complexes, pseudopodia and membrane ruffles. Both gonadotrophins trigger a rapid moesin and FAK activation via a non-genomic signaling cascade involving Gα13 protein, ROCK-2 to moesin and Gαi/β, c-Src to FAK. In conclusion, LH and FSH regulate BC cell movement by rapidly signaling to moesin and FAK via the actin cytoskeleton. These findings provide new information on the biological actions of gonadotrophins on BC cells as well as to open the path to new approaches to prevent or treat breast cancer disease in ageing, through the modulation of gonadotrophin actions.