INVESTIGADORES
JAHN Graciela Alma
congresos y reuniones científicas
Título:
Modulation of gonadotrophins on breast cancer cell movement via FAK and moesin.
Autor/es:
UZAIR ID; NEIRA FJ; FLAMINI MI; JAHN GA; SANCHEZ AM
Lugar:
Potrero de los Funes
Reunión:
Congreso; XXX Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2012
Institución organizadora:
Sociedad de Biología de Cuyo
Resumen:
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.