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Title

Implication of ΔNp73 in oxaliplatin resistance in colorectal cancer: Role of the autophagy pathway

AuthorsSantos-López, Jorge; Soldevilla, Beatriz ; Rodríguez-Cobos, Javier; Higuera, Oliver; Rodríguez, Nuria ; Domínguez, Gemma
Issue Date2019
Citation42nd Congress of the Spanish Society of Biochemistry and Molecular Biology (2019)
AbstractColorectal cancer (CRC) is one of the most prominent malignancies which reached the second highest mortality and 5-year prevalence and the third highest incidence worldwide in 2018. Its ve-year survival rate shows a strong dependence with the stage of the disease, ranging from 90% for patients with stage I to 10% for patients with stage IV. The intrinsic or acquired therapy resistance of cancer cells is an important cause for clinical fail in the management of advanced stages of this pathology. The study of the molecular mechanisms responsible for therapy resistance in CRC would allows us to design more e ective therapeutic strategies. Oxaliplatin is a platinum-based chemotherapeutic agent which exerts cytotoxic e ect mostly through DNA damage. This drug has been approved for the treatment of CRC, for example it has been used in the first-line chemotherapy strategy for metastatic CRC. The oxaliplatin resistance could contribute to bad clinical outcomes in advanced CRC. ΔNp73 is an oncogenic isoform of the TP53 family codi ed by the TP73 gene. We have previously observed that the transcription factor ΔNp73 positively regulates some genes implicated in drug resistance and autophagy and its expression increases with the CRC stage. Thus, we hypothesize that ΔNp73 could be implicated in oxaliplatin resistance of CRC. Thus, in this work, we have analyzed the role of ΔNp73 in oxaliplatin resistance of colorectal cancer cells through in vitro and in vivo approaches. The results obtained show that the overexpression of ΔNp73 is associated with oxaliplatin resistance and a higher basal and oxaliplatin-response autophagic flux in these cells. These results support our initial hypothesis and place autophagy as a possible molecular mechanism of oxaliplatin resistance induced by ΔNp73.
DescriptionResumen del póster presentado al 42nd Congress of the Spanish Society of Biochemistry and Molecular Biology (SEBBM), celebrado en Madrid del 16 al 19 de julio de 2019.
URIhttp://hdl.handle.net/10261/190342
Appears in Collections:(IIBM) Comunicaciones congresos
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