Antimo Migliaccio
Antimo Migliaccio
affiliation: Seconda Universita' di Napoli
research area(s): Cell Biology, Cancer Biology
Course: Molecular Pathology and Pathophysiology
University/Istitution: Università di Napoli Federico II
Antimo Migliaccio, got his M. D. degree at the University of Naples Federico II in the 1981. From 1984 to 1992 he held the position of Assistant Professor (Research) at I Medical School of University of Naples and starting from 1992 is Associate Professor of General Pathology at Medical Faculty of II University of Naples. In 1987 he worked at the LGME in Strasbourg under the supervision of Pierre Chambon. Dr. Migliaccio is intersted from beginning of his activity in the mechanism of action of steroid hormones. His activity has been initially focused on the mechanisms regulating the ligand binding activity of estrogen receptor. These studies led to observation that the estradiol receptor binding activity is regulated by a phosporylation-dephosphorylation process. In 1984 his studies led to observation that estrogen receptor phosphorylation responsible for hormone binding occurred only on a tyrosine residue at 537 position. Two enzymes: a nuclear tyrosine phosphatase and a cytosol tyrosine kinase have been identified and characterized . The kinase has been isolated and identified as a src like tyrosine kinase. Subsequently, the scientific activity of Dr. Migliaccio has been focused on the mechanisms by which estrogens regulate cell growth. His work has recently demonstrated that estrogens activate "src/ras/erk" transduction pathway. It has now observed that also progestins activate via a cross talk with estrogen receptor the same pathway, hereby suggesting that activation of src/ras/erk cascade can represent the main way by which steroid hormones stimulate cell growth. Since 2002 Dr. Migliaccio is a full Professor of General Pathology at II University of Naples. His studies are still focused on the mechanism of action of sex steroid hormones and have shown that a complex network including two signal transduction pathways, namely the src/ras/erk and PI3-K pathways, is responsible for hormone dependent DNA synthesis. On the basis of these findings, small molecule inhibitors have been set up to develop innovative strategies for the human hormone-dependent cancer therapy.
The current scientific activity of Dr. Migliaccio is focused on the role of sex steroid in unconventional target of hormone action such as fibroblasts and the mechanisms involved in the loss of hormone dependence of prostate cancer. In particular, recent evidence indicates that Androgen Receptor (AR) interacts with Filamin A in different cell types. Such an interaction has been observed in AR-rich epithelial cells (LNCaP, prostate carcinoma cell line) and more recently in NIH 3T3 mouse fibroblasts treated with androgens. Filamins are large (280 KDa) actin-binding proteins that stabilize three-dimensional actin filament networks and link them to cellular membranes where they integrate cell architectural and signaling functions: Filamin A is a scaffold protein interacting with a variety of signal transducers important for cell locomotion. Furthermore, recent findings draw emerging roles of filamins in cell signaling and transcription, with a phenotypic impact on cell motility or proliferation under different physiological or pathological conditions and organ development. Mutations in Filamin A are associated with human genetic diseases due to failure in cell migration and abnormal development of organs. Despite of these important potential implications the role of the interaction between AR and Filamin is still elusive.
Recent findings from our laboratory have shown that in NIH 3T3 cells physiological concentrations of androgens induce extranuclear AR interaction with the full-length (280 KDa) Filamin A promoting cell migration and inducing cell cycle arrest. Interestingly, our preliminary studies indicate that these hormones also exert an inhibitory effect on EGF induced S-phase entry of fibroblasts without affecting EGF-stimulated migration, whereas association between AR and a 90 KDa Filamin A fragment has been previously observed in prostate cancer cell, involved in AR dependent transcription and DNA synthesis stimulation. Our current activity is aimed to:
i. Analyze the molecular mechanism by which androgens or other growth factors induce association of AR with full-length Filamin A in fibroblasts and prostate cancer cells with different hormone-responsiveness;
ii. Assess the role of the AR/full-length Filamin A interaction in regulating cell cycle and motility, and dissect the pathway(s) involved in these actions;
iii. Investigate in animal models whether the interaction AR/Filamin-280KDa plays a major role in prostate cancer metastasis and in the loss of hormone responsive growth: we challenge the hypothesis that appearance of such a complex in the prostate cancer cells is associated with an aggressive, metastatic phenotype characterized by hormone independent growth and enhanced motility in response to androgens.
1. Giovannelli P, Di Donato M, Giraldi T, Migliaccio A, Castoria G, Auricchio F. (2011). Front Biosci.;17: 2224-32.
2. Castoria G, D'Amato L, Ciociola A, Giovannelli P, Giraldi T, Sepe L, Paolella G, Barone MV, Migliaccio A, Auricchio F. (2011). PLoS One.;6(2): e17218.
3. Giraldi T, Giovannelli P, Di Donato M, Castoria G, Migliaccio A, Auricchio F. (2010) J Cell Commun Signal.:161-72.
4. Migliaccio A, Castoria G, Giovannelli P, Auricchio F. (2010) Mol Cell Endocrinol. 327(1-2):19-24.
5. Castoria G, Migliaccio A, Giovannelli P, Auricchio F. (2010) Steroids. 75(8-9): 524-7. Review.
6. Castoria G, Migliaccio A, Auricchio F. (2009) Mol Cell Endocrinol. 308(1-2):26-31. Review.
7. Lombardi M, Castoria G, Migliaccio A, Barone MV, Di Stasio R, Ciociola A, Bottero D, Yamaguchi H, Appella E, Auricchio F. (2008) J Cell Biol. 182(2): 327-40.
8. Auricchio F, Migliaccio A, Castoria G. (2008) Steroids. 880-4.
9. Varricchio L, Migliaccio A, Castoria G, Yamaguchi H, de Falco A, Di Domenico M, Giovannelli P, Farrar W, Appella E, Auricchio F. (2007) Mol Cancer Res. 5(11): 1213-21.
10. Castoria G, Migliaccio A, D'Amato L, Di Stasio R, Ciociola A, Lombardi M, Bilancio A, Di Domenico M, de Falco A, Auricchio F. (2008) Front Biosci. 13:1318-27. Review.
11. Migliaccio A, Varricchio L, De Falco A, Castoria G, Arra C, Yamaguchi H, Ciociola A, Lombardi M, Di Stasio R, Barbieri A, Baldi A, Barone MV, Appella E, Auricchio F. (2007) Oncogene. 26(46):6619-29.
12. Migliaccio A, Castoria G, Auricchio F. (2007). Int J Biochem Cell Biol.; 39(7-8):1343-8. Review.
Project Title:
Androgen Receptor/Filamin interaction: its role in prostate cancer progression and metastasis.

Project Title:
Role of Androgen Receptor in hormone-resistant cells.