Androgen-Induced Cell Migration: Role of Androgen Receptor/Filamin A Association

Background: Androgen receptor (AR) controls male morphogenesis, gametogenesis and prostate growth as well as development of prostate cancer. These findings support a role for AR in cell migration and invasiveness. However, the molecular mechanism involved in AR-mediated cell migration still remains elusive. Methodology/Principal Findings: Mouse embryo NIH3T3 fibroblasts and highly metastatic human fibrosarcoma HT1080 cells harbor low levels of transcriptionally incompetent AR. We now report that, through extra nuclear action, AR triggers migration of both cell types upon stimulation with physiological concentrations of the androgen R1881. We analyzed the initial events leading to androgen-induced cell migration and observed that challenging NIH3T3 cells with 10 nM R1881 rapidly induces interaction of AR with filamin A (FlnA) at cytoskeleton. AR/FlnA complex recruits integrin beta 1, thus activating its dependent cascade. Silencing of AR, FlnA and integrin beta 1 shows that this ternary complex controls focal adhesion kinase (FAK), paxillin and Rac, thereby driving cell migration. FAK-null fibroblasts migrate poorly and Rac inhibition by EHT impairs motility of androgen-treated NIH3T3 cells. Interestingly, FAK and Rac activation by androgens are independent of each other. Findings in human fibrosarcoma HT1080 cells strengthen the role of Rac in androgen signaling. The Rac inhibitor significantly impairs androgen-induced migration in these cells. A mutant AR, deleted of the sequence interacting with FlnA, fails to mediate FAK activation and paxillin tyrosine phosphorylation in androgen-stimulated cells, further reinforcing the role of AR/FlnA interaction in androgen-mediated motility. Conclusions/Significance: The present report, for the first time, indicates that the extra nuclear AR/FlnA/integrin beta 1 complex is the key by which androgen activates signaling leading to cell migration. Assembly of this ternary complex may control organ development and prostate cancer metastasis

“ Betaxolol: Long Term Therapeutic Efficacy and Safety in patients with Bronchopneumopathy”

Efficacia a lungo termine del Betaxololo nei pazienti con broncopneumopati

"Betaxololo: efficacia e sicurezza nei pazienti glaucomatosi con broncopatia cronica ostruttiva" .

Betaxololo: efficacia e sicurezza nei pazienti glaucomatosi con broncopatia cronica ostruttiva"

“ Importanza dei fattori emodinamici nel follow-up della patologia glaucomatosa”

Influenza dei fattori emodinamici nel glaucoma ad angolo apert

"Betaxololo: efficacia e sicurezza nei pazienti glaucomatosi con broncopatia cronica ostruttiva" .

Betaxololo: efficacia e sicurezza nei pazienti glaucomatosi con broncopatia cronica ostruttiva"

"Betaxolol: long-term therapeutic efficacy and safety in glaucoma patients with chronic obstructive lung diseases".

The authors refer their experience with Betaxolol in the long-term treatment of open-angle glaucoma. The parameters considered were: ocular pressure, biomicroscopy of the eye anterior segment, systemic blood pressure, heart rate and static spirometric values ( prior to and after aerosol administration of the data obtained it was shown that betaxolol induces a long-term marked ocular hypotensive action ( 5 years of observation) without modifying lung function ( in asthmatic glaucomatous patients) and cardiocirculatory conditions. No adverse reactions, both topical and systemic, were ever noted

"Validità terapeutica a lungo termine del Dapripazolo nel trattamento del glaucoma ad angolo aperto"

Validità terapeutica a lungo termine del Dapripazolo nel trattamento del glaucoma ad angolo apert

"Timolol, Betaxolol und Befunolol in der Glaukombehandlung, Untersuchungüber die bronchopulmonalen Effekte".

Timolol, Betaxolol und Befunolol in der Glaukombehandlung, Untersuchungüber di

"Timololo, Betaxololo, Befunololo per via locale nel glaucoma: studio sugli effetti cardiovascolari e broncopolmonari".

Timololo, Betaxololo, Befunololo per via locale nel glaucoma: studio sugli effetti cardiovascolari e broncopolmonari