ROLE OF GONADOTROPHINS, LH AND FSH, ON BREAST CANCER CELL MOVEMENT VIA PHOSPHORYLATION OF FOCAL ADHESION KINASE AND MOESIN

A.M. SANCHEZ; M.I. FLAMINI; A.R. GENAZZANI; T. SIMONCINI

March 4-7, FIRENZE, ITALY.

Congreso; 14th World Congress of Gynecological Endocrinology, II Congresso ISGE Italia; 2010

INTERNATIONAL SOCIETY OF GYNECOLOGICAL ENDOCRINOLOGY (ISGE)

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 breast cancer 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 breast cancer 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 G alpha13 protein, ROCK-2 to moesin and G alpha i/beta, c-Src to FAK. In conclusion, LH and FSH regulate breast cancer 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 breast cancer 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.