Journal article

Mutant p53 upregulates alpha-1 antitrypsin expression and promotes invasion in lung cancer

R Shakya, GA Tarulli, L Sheng, NA Lokman, C Ricciardelli, KI Pishas, CI Selinger, MRJ Kohonen-Corish, WA Cooper, AG Turner, PM Neilsen, DF Callen

Oncogene | NATURE PUBLISHING GROUP | Published : 2017

Abstract

Missense mutations in the TP53 tumor-suppressor gene inactivate its antitumorigenic properties and endow the incipient cells with newly acquired oncogenic properties that drive invasion and metastasis. Although the oncogenic effect of mutant p53 transcriptome has been widely acknowledged, the global influence of mutant p53 on cancer cell proteome remains to be fully elucidated. Here, we show that mutant p53 drives the release of invasive extracellular factors (the 'secretome') that facilitates the invasion of lung cancer cell lines. Proteomic characterization of the secretome from mutant p53-inducible H1299 human non-small cell lung cancer cell line discovered that the mutant p53 drives its ..

View full abstract

Grants

Awarded by NHMRC Project


Funding Acknowledgements

We thank TCGA research network for publicly sharing their data. The results published here are in part based upon data generated by the TCGA project, which was established by the NCI and NHGRI. Information about TCGA and the investigators and institutions who constitute the TCGA research network can be found at http://cancergenome.nih.gov. We also thank Rebecca C Haycox for her technical assistance. This work was supported by the NHMRC Project grants (44107714 and 44112162). K Pishas acknowledges financial contributions from the University of Adelaide Florey Medical Research Foundation Clinical Cancer Research Fellowship.