Molecular and proteomic insight into Notch1 characterization in hepatocellular carcinoma

Catia Giovannini; Manuela Minguzzi; Filippo Genovese; Michele Baglioni; Alessandra Gualandi; Matteo Ravaioli; Maddalena Milazzo; Simona Tavolari; Luigi Bolondi; Laura Gramantieri

doi:10.18632/oncotarget.9203

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Research Papers:

Molecular and proteomic insight into Notch1 characterization in hepatocellular carcinoma

Catia Giovannini _, Manuela Minguzzi, Filippo Genovese, Michele Baglioni, Alessandra Gualandi, Matteo Ravaioli, Maddalena Milazzo, Simona Tavolari, Luigi Bolondi and Laura Gramantieri

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Oncotarget. 2016; 7:39609-39626. https://doi.org/10.18632/oncotarget.9203

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Abstract

Catia Giovannini1,2, Manuela Minguzzi1,2, Filippo Genovese1,3, Michele Baglioni1, Alessandra Gualandi1,3, Matteo Ravaioli4, Maddalena Milazzo1, Simona Tavolari1,5, Luigi Bolondi1,2, Laura Gramantieri1

1Center for Applied Biomedical Research (CRBA), S.Orsola-Malpighi University Hospital, Bologna, Italy

2Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy

3C.I.G.S., University of Modena and Reggio Emilia, Bologna, Italy

4Department of Medical and Surgical Sciences, General and Transplant Surgery Unit, University of Bologna, Bologna, Italy

5Department of Experimental Diagnostic Specialty Medicine, University of Bologna, Bologna, Italy

Correspondence to:

Catia Giovannini, email: [email protected]

Keywords: Notch1, invasion, proteomic, markers, HCC

Received: July 24, 2015 Accepted: April 10, 2016 Published: May 06, 2016

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.

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Research Papers:

Molecular and proteomic insight into Notch1 characterization in hepatocellular carcinoma

Abstract