Involvement of AF1q/MLLT11 in the progression of ovarian cancer
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Paola Tiberio1, Ludmila Lozneanu1,2, Valentina Angeloni1, Elena Cavadini1, Patrizia Pinciroli3, Maurizio Callari1,4, Maria Luisa Carcangiu5, Domenica Lorusso6, Francesco Raspagliesi6, Valentina Pala1, Maria Grazia Daidone1, Valentina Appierto1
1Department of Experimental Oncology and Molecular Medicine, Biomarkers Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
2Department of Morphofunctional Sciences–Histology, Patology, “Grigore T. Popa” University of Medicine and Pharmacy, Iassy, Romania
3Department of Experimental Oncology and Molecular Medicine, Functional Genomics Facility, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
4Present address: Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom
5Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
6Department of Surgery, Gynecologic Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
Valentina Appierto, email: firstname.lastname@example.org
Keywords: AF1q/MLLT11, ovarian cancer, borderline ovarian tumor/BOT, low malignant potential ovarian tumor, EMT
Received: January 26, 2016 Accepted: February 12, 2017 Published: February 21, 2017
The functional role of AF1q/MLLT11, an oncogenic factor involved in a translocation t(1;11)(q21;q23) responsible for acute myeloid leukaemia, has been investigated in hematological and solid malignancies and its expression was found to be linked to tumor progression and poor clinical outcome. In addition to its oncogenic function, AF1q has been shown to play a role in the onset of basal and drug-induced apoptosis in cancer cells of different histotypes, including ovarian cancer. Through in vitro, ex vivo, and in silico approaches, we demonstrated here that AF1q is also endowed with protumorigenic potential in ovarian cancer. In ovarian cancer cell lines, stable AF1q overexpression caused activation of epithelial-to-mesenchymal transition and increased motility/migratory/invasive abilities accompanied by gene expression changes mainly related to Wnt signaling and to signaling pathways involving in ERK/p38 activation. The potential role of AF1q in ovarian cancer progression was confirmed by immunohistochemical and in silico analyses performed in ovarian tumor specimens which revealed that the protein was absent in normal ovarian epithelium and became detectable when atypical proliferation was present. Moreover, AF1q was significantly lower in borderline ovarian tumors (i.e., tumors of low malignant potential without stromal invasion) than in invasive tumors, thus corroborating the association between high AF1q expression and increased migratory/invasive cell behavior and confirming its potential role in ovarian cancer progression. Our findings demonstrated, for the first time, that AF1q is endowed with protumorigenic activity in ovarian cancer, thus highlighting a dual behavior (i.e., protumorigenic and proapoptotic functions) of the protein in the malignancy.
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