A mutant p53/Hif1α/miR-30d axis reprograms the secretory pathway promoting the release of a prometastatic secretome
Authors:Valeria Capaci1,2, Fiamma Mantovani1 and Giannino Del Sal1,2,3
1 Dipartimento di Scienze della Vita, Università degli Studi di Trieste – Trieste (TS), 34127 – Italy.
2 Cancer Cell Signalling, International Centre for Genetic Engineering and Biotechnology- Trieste (TS), 34149 – Italy.
3 Fondazione Istituto FIRC di Oncologia Molecolare (IFOM) – Milan (MI), 20139 – Italy.
Keywords:
mutant p53, miR-30d, Golgi Apparatus, secretory machinery, microenvironment.
Corresponding Author(s):
Conflict of interest statement:
The authors declare no potential conflicts of interest.
Please cite this article as:
Valeria Capaci, Fiamma Mantovani and Giannino Del Sal (2020). A mutant p53/Hif1α/miR-30d axis reprograms the secretory pathway promoting the release of a prometastatic secretome. Cell Stress 4(11): 261-264. doi: 10.15698/cst2020.11.235
© 2020 Capaci et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduc-tion in any medium, provided the original author and source are acknowledged.
Abstract:
TP53 missense mutations are frequent driver events during tumorigenesis. The majority of TP53 mutations are missense and occur within the DNA binding domain of p53, leading to expression of mutant p53 (mut-p53) proteins that not only lose the tumor suppressive functions of the wild-type (wt-p53) form, but can also acquire novel oncogenic features fostering tumor growth, metastasis and chemoresistance. Mut-p53 affects fundamental cellular pathways and functions through different mechanisms, a major one being the alteration of gene expression. In our recent work (Capaci et al., 2020, Nat Commun) we found that mut-p53, via miR-30d, modifies structure and function of the Golgi apparatus (GA) and induces increased rate of trafficking. This culminates in the release of a pro-malignant secretome, which is capable of remodeling the tumor microenvironment (TME), to increase stiffness of the extracellular matrix (ECM), favouring metastatic colonization, as shown by cell-based assays and experiments of metastatic niche preconditioning in mouse xenograft models. This study provides new insights into the mechanisms by which mut-p53, through induction of non-coding RNAs, can exert pro-tumorigenic functions in a non-cell-autonomous fashion, and highlights potential non-invasive biomarkers and therapeutic targets to treat tumors harboring mut-p53 (Figure 1).