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A balancing act: orchestrating amino-truncated and full-length p73 variants as decisive factors in cancer progression

Oncogene volume 34, pages 4287–4299 (2015)Cite this article

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Abstract

p73 is the older sibling of p53 and mimics most of its tumor-suppressor functions. Through alternative promoter usage and splicing, the TP73 gene generates more than two dozen isoforms of which N-terminal truncated DNp73 variants have a decisive role in cancer pathogenesis as they outweigh the positive effects of full-length TAp73 and p53 in acting as a barrier to tumor development. Beyond the prevailing view that DNp73 predominantly counteract cell cycle arrest and apoptosis, latest progress indicates that these isoforms acquire novel functions in epithelial-to-mesenchymal transition, metastasis and therapy resistance. New insight into the mechanisms underlying this behavior reinforced the expectation that DNp73 variants contribute to aggressive cellular traits through both loss of wild-type tumor-suppressor activity and gain-of-function, suggesting an equally important role in cancer progression as mutant p53. In this review, we describe the novel properties of DNp73 in the invasion metastasis cascade and outline the comprehensive p73 regulatome with an emphasis on molecular processes putting TAp73 out of action in advanced tumors. These intriguing insights provoke a new understanding of the acquisition of aggressive traits by cancer cells and may help to set novel therapies for a broad range of metastatic tumors.

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Acknowledgements

This work was supported by funds from the German Cancer Aid, Federal Ministry of Education and Research as part of the project eBio:SysMet and FORUN program of Rostock University Medical Center. We apologize to colleagues whose studies we did not cite owing to space limitations.

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    D Engelmann, C Meier, V Alla & B M Pützer

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Engelmann, D., Meier, C., Alla, V. et al. A balancing act: orchestrating amino-truncated and full-length p73 variants as decisive factors in cancer progression. Oncogene 34, 4287–4299 (2015). https://doi.org/10.1038/onc.2014.365

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