Sex steroid actions on the cytoskeleton and movement in breast cancer cells.

X. FU; M.S. GIRETTI; L. GOGLIA; C. BALDACCI; S. GARIBALDI; A.M. SANCHEZ; M. FLAMINI; P. MANNELLA; A.R. GENAZZANI; T. SIMONCINI

February 28-March 2, Florence, Italy

Congreso; 13th World Congress of Gynecological Endocrinology.; 2008

Estrogen and progesterone play a critical role in mammary development but also in breast cancer progression. However, there is a general lack of information  on the role plaid by sex steroids on cancer cell migration and invasion that are relevant to metastasis. To this extent, we studied the effects of 17beta-estradiol and progesterone on cell movement and invasion via the regulation of actin regulatory proteins as well as of the formation of adhesion structures, such as focal adhesion complexes. Estradiol and progesterone are associated with rapid and dynamic actin cytoskeleton remodelling and with the dynamic formation of focal adhesion complexes. These phenomena are linked with ER+/PR+ breast cancer cell movement and invasion of three-dimensional matrices. The signaling involved in these processes is based on rapid activation of signaling pathways within the cell membrane or in the cytoplasm. For instance, the activation of the actin regulatory protein moesin depends on the interaction of cell membrane-ERá or PRA with the G protein Gá13, which results in the recruitment of a Rho-A and Rho-associated kinase (ROCK)-dependent moesin phosphorylation. Similar rapid actions are found which target focal adhesion kinase (FAK). Studies on human breast cancers indicate that some of these original molecular signaling of sex steroids may be relevant in the clinical setting. In fact, moesin seems to be over-expressed and activated in cancers with higher metastasizing potential. In conclusion, sex steroids enhance breast cancer cell movement and invasion by targeting the actin cytoskeleton and the formation of adhesion  tructures. These results provide new evidence on the molecular signaling of estrogen related to breast cancer metastasis and the pathways described may represent therapeutical targets to interfere with steroid-dependent breast cancer cell metastasis.