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

• Published in: Oncotarget Vol. 7; no. 12; pp. 14765 - 14780
• Main Authors: Murdocca, Michela, Mango, Ruggiero, Pucci, Sabina, Biocca, Silvia, Testa, Barbara, Capuano, Rosamaria, Paolesse, Roberto, Sanchez, Massimo, Orlandi, Augusto, di Natale, Corrado, Novelli, Giuseppe, Sangiuolo, Federica
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 22-03-2016
• Subjects: Adenocarcinoma - metabolism; Adenocarcinoma - secondary; Aged; Biomarkers, Tumor - metabolism; Cell Movement; Cell Proliferation; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Female; Follow-Up Studies; Humans; Lymphatic Metastasis; Male; Neoplasm Staging; Prognosis; Research Paper; Scavenger Receptors, Class E - metabolism; Survival Rate; Tumor Cells, Cultured; LOX-1; colon cancer; shRNAs; VOCs analysis
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.7430

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.