TAp73 upregulates IL-1β in cancer cells: Potential biornarker in lung and breast cancer?

p73 is a transcription factor belonging to the p53 tumour suppressor family. p73(-/-) mice exhibit a range of phenotypes including neurological, reproductive and inflammatory defects. Although the role of p73 in the control of genomic stability explains part of these phenotypes, a clear mechanism of how p73 participates in the inflammatory response is still elusive. Interleukin-1 beta (IL-1 beta) has a crucial role in mediating the inflammatory response. Because of its high potency to induce inflammation, the activation and secretion of IL-1 beta is tightly regulated by large protein complexes, named inflammasomes. Inflammasomes regulate activation of proinflammatory caspase-1, which in turn proteolytically processes its substrates, including pro-IL-1 beta. Caspase-1 gene transcription is strongly activated by p53 protein family members including p73. Here, we have addressed whether p73 might be directly involved in IL-1 beta regulation and therefore in the control of the inflammatory response. Our results show that TAp73 beta upregulates pro-IL-1 beta mRNA and processed IL-1 beta protein. In addition, analysis of breast and lung cancer patient cohorts demonstrated that interaction between p73 and IL-1 beta predicts a negative survival outcome in these human cancers. (C) 2016 The Author(s). Published by Elsevier Inc.