A novel role for the tumor suppressor gene ITF2 in lung tumorigenesis through the action of Wnt signaling pathway

Despite often leading to a platinum resistance, Platinum-based chemotherapy continues to be the standard treatment for non-small cell lung cancer (NSCLC) and ovarian cancer. In this study, we used array-CGH and qRT-PCR methodologies to identify and validate cytogenetic alterations that arise after cisplatin treatment in four paired cisplatin-sensitive/resistant cell lines. We found the presence of a common deletion of the gene ITF2 in cisplatin-resistant cell lines. Our translational approach included the expression analysis in a total of 35 lung and ovarian primary tumors, showing a frequent downregulation of ITF2. Whole transcriptome sequencing (RNA- seq) and Wnt-pathway analysis in a subgroup of NSCLC patients identified four genes with a potential role in the development of this malignancy. Further functional assays overexpressing ITF2 in NSCLC cisplatin-resistant cells suggest the regulation of HOXD9 by the Wnt pathway and its implication on NSCLC progression.