Oncotarget

Research Papers:

The lectin-like oxidized LDL receptor-1: a new potential molecular target in colorectal cancer

Michela Murdocca _, Ruggiero Mango, Sabina Pucci, Silvia Biocca, Barbara Testa, Rosamaria Capuano, Roberto Paolesse, Massimo Sanchez, Augusto Orlandi, Corrado di Natale, Giuseppe Novelli and Federica Sangiuolo

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Oncotarget. 2016; 7:14765-14780. https://doi.org/10.18632/oncotarget.7430

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Abstract

Michela Murdocca1, Ruggiero Mango2, Sabina Pucci1, Silvia Biocca3, Barbara Testa1, Rosamaria Capuano4, Roberto Paolesse5, Massimo Sanchez6, Augusto Orlandi1, Corrado di Natale4, Giuseppe Novelli1, Federica Sangiuolo1

1Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy

2Department of Emergency and Critical Care, Section of Cardiology, Policlinic of Tor Vergata, Rome, Italy

3Department of Systems Medicine, Tor Vergata University, Rome, Italy

4Department of Electronic Engineering, Tor Vergata University, Rome, Italy

5Department of Chemical Science and Technology, Tor Vergata University, Rome, Italy

6Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy

Correspondence to:

Federica Sangiuolo, e-mail: [email protected]

Keywords: colon cancer, LOX-1, VOCs analysis, shRNAs

Received: July 28, 2015     Accepted: January 29, 2016     Published: February 17, 2016

ABSTRACT

The identification of new biomarkers and targets for tailored therapy in human colorectal cancer (CRC) onset and progression is an interesting challenge.

CRC tissue produces an excess of ox-LDL, suggesting a close correlation between lipid dysfunction and malignant transformation. Lectin-like oxidized LDL receptor-1 (LOX-1) is involved in several mechanisms closely linked to tumorigenesis.

Here we report a tumor specific LOX-1 overexpression in human colon cancers: LOX-1 results strongly increased in the 72% of carcinomas (P<0.001), and strongly overexpressed in 90% of highly aggressive and metastatic tumours (P<0.001), as compared to normal mucosa. Moreover LOX-1 results modulated since the early stage of the disease (adenomas vs normal mucosa; P<0.001) suggesting an involvement in tumor insurgence and progression.

The in vitro knockdown of LOX-1 in DLD-1 and HCT-8 colon cancer cells by siRNA and anti-LOX-1 antibody triggers to an impaired proliferation rate and affects the maintenance of cell growth and tumorigenicity. The wound-healing assay reveals an evident impairment in closing the scratch. Lastly knockdown of LOX-1 delineates a specific pattern of volatile compounds characterized by the presence of a butyrate derivative, suggesting a potential role of LOX-1 in tumor-specific epigenetic regulation in neoplastic cells.

The role of LOX-1 as a novel biomarker and molecular target represents a concrete opportunity to improve current therapeutic strategies for CRC. In addition, the innovative application of a technology focused to the identification of LOX-1 driven volatiles specific to colorectal cancer provides a promising diagnostic tool for CRC screening and for monitoring the response to therapy.


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