title: Molecular and proteomic insight into Notch1 characterization in hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) ranks fifth in frequency worldwide amongst all human cancers causing one million deaths annually. Despite many promising treatment options, long-term prognosis remains dismal for the majority of patients who develop recurrence or present with advanced disease. Notch signaling is an evolutionarily conserved pathway crucial for the development and homeostasis of many organs including liver. Herein we showed that aberrant Notch1 is linked to HCC development, tumor recurrence and invasion, which might be mediated, at least in part, through the Notch1-E-Cadherin pathway. Collectively, these findings suggest that targeting Notch1 has important therapeutic value in hepatocellular carcinoma. In this regard, comparative analysis of the secretome of HepG2 and HepG2 Notch1 depleted cells identified novel secreted proteins related to Notch1 expression. Soluble E-Cadherin (sE-Cad) and Thrombospondin-1 (Thbs1) were further validated in human serum as potential biomarkers to predict response to Notch1 inhibitors for a tailored individualized therapy.
authors.affiliation: Center for Applied Biomedical Research (CRBA), S.Orsola-Malpighi University Hospital, Bologna, Italy.|Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
authors.forename: Catia
authors.initials: C
authors.lastname: Giovannini
authors.affiliation: Center for Applied Biomedical Research (CRBA), S.Orsola-Malpighi University Hospital, Bologna, Italy.|Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Minguzzi
authors.affiliation: Center for Applied Biomedical Research (CRBA), S.Orsola-Malpighi University Hospital, Bologna, Italy.|C.I.G.S., University of Modena and Reggio Emilia, Bologna, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Genovese
authors.affiliation: Center for Applied Biomedical Research (CRBA), S.Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Baglioni
authors.affiliation: Center for Applied Biomedical Research (CRBA), S.Orsola-Malpighi University Hospital, Bologna, Italy.|C.I.G.S., University of Modena and Reggio Emilia, Bologna, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gualandi
authors.affiliation: Department of Medical and Surgical Sciences, General and Transplant Surgery Unit, University of Bologna, Bologna, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Ravaioli
authors.affiliation: Center for Applied Biomedical Research (CRBA), S.Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Milazzo
authors.affiliation: Center for Applied Biomedical Research (CRBA), S.Orsola-Malpighi University Hospital, Bologna, Italy.|Department of Experimental Diagnostic Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Tavolari
authors.affiliation: Center for Applied Biomedical Research (CRBA), S.Orsola-Malpighi University Hospital, Bologna, Italy.|Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Bolondi
authors.affiliation: Center for Applied Biomedical Research (CRBA), S.Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Gramantieri
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D015820:Cadherins / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned / Q000737:chemistry; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D040901:Proteomics / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D051881:Receptor, Notch1 / Q000378:metabolism*; D015398:Signal Transduction; D019700:Thrombospondin 1 / Q000097:blood; D014945:Wound Healing
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; D015820:Cadherins; D017077:Culture Media, Conditioned; D005819:Genetic Markers; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D019700:Thrombospondin 1
keywords: HCC; Notch1; invasion; markers; proteomic