Epidermal growth factor (EGF) partly compensates the lack of FAK and SHP-1 during PC3 cell migration

JAVIER RODRIGUEZ-UBREVA; ARIEL E. CARIAGA-MARTINEZ; M. ALICIA CORTÉS; PILAR LÓPEZ-RUIZ; BEGOÑA COLÁS

Vienna

Congreso; 32nd FEBS Molecular Machines; 2007

Febs

It is well known that metastasis is the cause of morbidity and mor- tality in patients with cancer. Prostate cancer cells have a propen- sity to metastasize to bone. This metastatic process is partly controlled by tyrosine kinases and tyrosine phosphatases and results from complex interactions between epithelium, stroma and multiple growth factors. Thus, we analyzed the role of tyrosine phosphatase SHP-1, tyrosine kinase FAK and epidermal growth factor (EGF) in the regulation of cellular adhesion and migration on collagen type I, the major bone extracellular matrix component. Our results show that in human prostatic PC3 cancer cells, SHP-1 colocalizes with FAK in membrane lamellipodia, both proteins being constitutively associated during cell adhesion and spreading on collagen type I. Furthermore, the decrease of SHP-1 or FAK expression by siRNA reduces basal cell transmigration, but poten- ciates EGF-induced transmigration, coinciding with an up-regula- tion of EGFR downstream signalling pathways, such as PI3K/Akt and p44/42. In summary, our observations suggest the possible existence of a mechanism in which EGF would partly compensate the reduction of FAK or SHP-1 during the cell migration process. This compensative mechanism could be due to a negative modula- tion by FAK via SHP-1, in the EGFR pathway.