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Zinc-dependent Zip7-MAZ-MYBL2 axis promotes prostate cancer metastasis

ABSTRACT: Screening reveals that a zinc transporter Zip7 was upregulated in metastatic PCa and related to poor progression. Zip7 silencing inhibits PCa cell migration and invasion in vitro and bone-metastasis in vivo. Mechanistically, we identify that Zip7 mainly interacts with MAZ in cytoplasm to facilitate MAZ nuclear import and nuclear MAZ was up-regulated in metastatic prostate cancer tissues and positively associated with Zip7 expression, which promotes PCa bone metastasis. Furthermore, our RNA-seq studies reveal that Zip7 facilitates MAZ nuclear import to promote MYBL2 transcription. Strikingly, we show in intraarterial injected-bone metastasis xenograft model that targeting Zip7 by its inhibitor markedly suppressed PCa bone metastasis. Collectively, our findings identify Zip7 is an important regulator of PCa metastasis and targeting Zinc-dependent Zip7-MAZ-MYBL2 could be a valuable strategy to ameliorate advanced PCa metastasis.

ORGANISM(S): Homo Sapiens

SUBMITTER: Bin Fu

PROVIDER: PXD073047 | iProX | Wed Jan 14 00:00:00 GMT 2026

REPOSITORIES: iProX

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Project description:This a model from the article: The dynamic balance of import and export of zinc in Escherichia coli suggests a heterogeneous population response to stress Takahashi H, Oshima T, Doherty N, Clayton SR, Iqbal M, Hill PJ, Hobman JL, Tobe T, Ogasawara N, Kanaya S and Stekel DJ journal year id, Abstract: Zinc is essential for life, but toxic in excess. Thus all cells must control their internal zinc concentration. We used a systems approach, alternating rounds of experiments and models, to further elucidate the zinc control systems in Escherichia coli. We measured the response to zinc of the main specific zinc import and export systems in the wild type, and a series of deletion mutant strains. We interpreted these data with a detailed mathematical model and Bayesian model fitting routines. There are three key findings: First, that alternate, non-inducible importers and exporters are important. Second, that an internal zinc reservoir is essential for maintaining the internal zinc concentration. Third, our data fitting led us to propose that the cells mount a heterogeneous response to zinc: some respond effectively, while others die or stop growing. In a further round of experiments we demonstrated lower viable cell counts in the mutant strain tested exposed to excess zinc, consistent with this hypothesis. A stochastic model simulation demonstrated considerable fluctuations in the cellular levels of the ZntA exporter protein, reinforcing this proposal. We hypothesise that maintaining population heterogeneity could be a bet-hedging response allowing a population of cells to survive in varied and fluctuating environments. This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. For more information see the terms of use. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le NovÃ¨re N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

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Zinc-dependent Zip7-MAZ-MYBL2 axis promotes prostate cancer metastasis

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