References of "CUSUMANO, Giuseppe"
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See detailMyoferlin regulates cellular lipid metabolism and promotes metastases in triple-negative breast cancer
Blomme, Arnaud; Costanza, Brunella ULg; De Tullio, Pascal ULg et al

in Oncogene (2016)

Myoferlin is a multiple C2-domain-containing protein that regulates membrane repair, tyrosine kinase receptor function and endocytosis in myoblasts and endothelial cells. Recently it has been reported as ... [more ▼]

Myoferlin is a multiple C2-domain-containing protein that regulates membrane repair, tyrosine kinase receptor function and endocytosis in myoblasts and endothelial cells. Recently it has been reported as overexpressed in several cancers and shown to contribute to proliferation, migration and invasion of cancer cells. We have previously demonstrated that myoferlin regulates epidermal growth factor receptor activity in breast cancer. In the current study, we report a consistent overexpression of myoferlin in triple-negative breast cancer cells (TNBC) over cells originating from other breast cancer subtypes. Using a combination of proteomics, metabolomics and electron microscopy, we demonstrate that myoferlin depletion results in marked alteration of endosomal system and metabolism. Mechanistically, myoferlin depletion caused impaired vesicle traffic that led to a misbalance of saturated/unsaturated fatty acids. This provoked mitochondrial dysfunction in TNBC cells. As a consequence of the major metabolic stress, TNBC cells rapidly triggered AMP activated protein kinase-mediated metabolic reprogramming to glycolysis. This reduced their ability to balance between oxidative phosphorylation and glycolysis, rendering TNBC cells metabolically inflexible, and more sensitive to metabolic drug targeting in vitro. In line with this, our in vivo findings demonstrated a significantly reduced capacity of myoferlin-deficient TNBC cells to metastasise to lungs. The significance of this observation was further supported by clinical data, showing that TNBC patients whose tumors overexpress myoferlin have worst distant metastasis-free and overall survivals. This novel insight into myoferlin function establishes an important link between vesicle traffic, cancer metabolism and progression, offering new diagnostic and therapeutic concepts to develop treatments for TNBC patients. [less ▲]

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See detailAsporin Is a Fibroblast-Derived TGF-beta1 Inhibitor and a Tumor Suppressor Associated with Good Prognosis in Breast Cancer.
Maris, Pamela; Blomme, Arnaud; Palacios, Ana Perez et al

in PLoS medicine (2015), 12(9), 1001871

BACKGROUND: Breast cancer is a leading malignancy affecting the female population worldwide. Most morbidity is caused by metastases that remain incurable to date. TGF-beta1 has been identified as a key ... [more ▼]

BACKGROUND: Breast cancer is a leading malignancy affecting the female population worldwide. Most morbidity is caused by metastases that remain incurable to date. TGF-beta1 has been identified as a key driving force behind metastatic breast cancer, with promising therapeutic implications. METHODS AND FINDINGS: Employing immunohistochemistry (IHC) analysis, we report, to our knowledge for the first time, that asporin is overexpressed in the stroma of most human breast cancers and is not expressed in normal breast tissue. In vitro, asporin is secreted by breast fibroblasts upon exposure to conditioned medium from some but not all human breast cancer cells. While hormone receptor (HR) positive cells cause strong asporin expression, triple-negative breast cancer (TNBC) cells suppress it. Further, our findings show that soluble IL-1beta, secreted by TNBC cells, is responsible for inhibiting asporin in normal and cancer-associated fibroblasts. Using recombinant protein, as well as a synthetic peptide fragment, we demonstrate the ability of asporin to inhibit TGF-beta1-mediated SMAD2 phosphorylation, epithelial to mesenchymal transition, and stemness in breast cancer cells. In two in vivo murine models of TNBC, we observed that tumors expressing asporin exhibit significantly reduced growth (2-fold; p = 0.01) and metastatic properties (3-fold; p = 0.045). A retrospective IHC study performed on human breast carcinoma (n = 180) demonstrates that asporin expression is lowest in TNBC and HER2+ tumors, while HR+ tumors have significantly higher asporin expression (4-fold; p = 0.001). Assessment of asporin expression and patient outcome (n = 60; 10-y follow-up) shows that low protein levels in the primary breast lesion significantly delineate patients with bad outcome regardless of the tumor HR status (area under the curve = 0.87; 95% CI 0.78-0.96; p = 0.0001). Survival analysis, based on gene expression (n = 375; 25-y follow-up), confirmed that low asporin levels are associated with a reduced likelihood of survival (hazard ratio = 0.58; 95% CI 0.37-0.91; p = 0.017). Although these data highlight the potential of asporin to serve as a prognostic marker, confirmation of the clinical value would require a prospective study on a much larger patient cohort. CONCLUSIONS: Our data show that asporin is a stroma-derived inhibitor of TGF-beta1 and a tumor suppressor in breast cancer. High asporin expression is significantly associated with less aggressive tumors, stratifying patients according to the clinical outcome. Future pre-clinical studies should consider options for increasing asporin expression in TNBC as a promising strategy for targeted therapy. [less ▲]

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See detailEuropean inter-institutional impact study of MammaPrint
CUSUMANO, Giuseppe ULg; Generali, D; Ciruelos, E et al

Poster (2012)

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See detailHormonothérapie du cancer du sein
LIFRANGE, Eric ULg; ANDRE, Chantal ULg; BLERET, Valerie ULg et al

in Revue Médicale de Liège (2011), 66(5-6), 367-371

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See detailPrise en charge et suivi d'une série consécutive de 411 patientes opérées pour cancer du sein
LIFRANGE, Eric ULg; ANDRE, Chantal ULg; BLERET, Valerie ULg et al

in Revue Médicale de Liège (2011), 66(5-6), 329-335

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See detailThe cancer screening controversy
CUSUMANO, Giuseppe ULg; LIFRANGE, Eric ULg

in European Journal of Cancer Prevention (2011), Suppl 1(S1),

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See detailL'observance au traitement de longue durée : le cas particulier de l'hormonothérapie adjuvante du cancer du sein
Bleret, Valerie ULg; Collignon, Joëlle ULg; Coucke, Philippe ULg et al

in Revue Médicale de Liège (2010), 65(5-6), 405-408

L'objectif de l'hormonothérapie adjuvante dans le cancer du sein est d'atteindre en pratique quotidiennee, une efficacité comparable à celle obtenue au cours des études cliniques. Malgré l'efficacité ... [more ▼]

L'objectif de l'hormonothérapie adjuvante dans le cancer du sein est d'atteindre en pratique quotidiennee, une efficacité comparable à celle obtenue au cours des études cliniques. Malgré l'efficacité démontrée de l'hormonothérapie, la compliance constitue un défi majeur et un problème multidimensionnel. Une meilleure compréhension des raisons de cette non-compliance aiderait à mieux identifier les patientes à risque et à développer des interventions capables d'améliorer l'adhésion à l'hormonothérapie adjuvante.C'est dans ce but que nous avons entrepris une revue de la littérature des six dernières années (Pub Med 2003-2006). [less ▲]

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