III. ATIP3 is a novel therapeutic target against breast cancer.
Breast cancer is a heterogeneous disease. Over the past decade, the classification of breast tumors into different molecular subtypes has led to the development of efficient personalized therapies against tumors that express hormone receptors and/or the ERBB2 oncogene. A major challenge for the future is to identify new molecular markers for a particular subset of breast tumors, designated triple-negative, that do not express neither hormone receptors nor ERBB2. Triple negative breast tumors are highly proliferative and metastatic, they do not respond to available targeted therapies and are thus considered of poor prognosis.
Studies of our lab conducted in collaboration with the Hospital and Institut Curie have shown that ATIP3, the major product of candidate tumor suppressor gene MTUS1, is a new molecular biomarker down-regulated in breast tumors. ATIP3 levels are reduced in 47% of invasive breast cancer, and in 85% of triple negative breast tumors. Importantly, ATIP3-re-expression into cancer cells delays the progression of mitosis and markedly reduces cell proliferation in vitro and tumor growth in vivo. At the molecular level, we have shown for the first time that ATIP3 closely associates with the microtubule cytoskeleton a key regulator of cell division and migration.
ATIP3 thus represents a new biomarker and therapeutic target for molecular therapies of breast tumors of poor prognosis
Our ongoing projects aim at identifying the functional domain of ATIP3 and elucidating the molecular mechanisms by which ATIP3 inhibits cell proliferation and tumor progression. These studies should ultimately lead to the development of new targeted therapies against a subpopulation of triple negative breast tumors that have lost ATIP3.
Tumor growth in vivo:
ATIP3 is a microtubule-associated protein:
- Molina A, Rodrigues-Ferreira S, Di Tommaso A, Nahmias C. ATIP, a novel superfamily of microtubule-associated proteins. Med Sci (Paris) 27(3):244-6 (2011). French.
- Rodrigues-Ferreira S, Nahmias C. An ATIPical family of angiotensin II AT2 receptor-interacting proteins. Trends Endocrinol Metab. 21(11):684-90 (2010). Review.
- Rodrigues-Ferreira S, Di Tommaso A, Dimitrov A, Cazaubon S, Gruel N, Colasson H, Nicolas A, Chaverot N, Molinié V, Reyal F, Sigal-Zafrani B, Terris B, Delattre O, Radvanyi F, Perez F, Vincent-Salomon A, Nahmias C. 8p22 MTUS1 gene product ATIP3 is a novel anti-mitotic protein underexpressed in invasive breast carcinoma of poor prognosis. PLoS One. 4(10):e7239 (2009). http://www.ncbi.nlm.nih.gov/pubmed/19794912