Science and Research

Extracellular Vesicles: Messengers of p53 in Tumor-Stroma Communication and Cancer Metastasis

Tumor progression to a metastatic and ultimately lethal stage relies on a tumor-supporting microenvironment that is generated by reciprocal communication between tumor and stromal host cells. The tumor-stroma crosstalk is instructed by the genetic alterations of the tumor cells-the most frequent being mutations in the gene Tumor protein p53 (TP53) that are clinically correlated with metastasis, drug resistance and poor patient survival. The crucial mediators of tumor-stroma communication are tumor-derived extracellular vesicles (EVs), in particular exosomes, which operate both locally within the primary tumor and in distant organs, at pre-metastatic niches as the future sites of metastasis. Here, we review how wild-type and mutant p53 proteins control the secretion, size, and especially the RNA and protein cargo of tumor-derived EVs. We highlight how EVs extend the cell-autonomous tumor suppressive activity of wild-type p53 into the tumor microenvironment (TME), and how mutant p53 proteins switch EVs into oncogenic messengers that reprogram tumor-host communication within the entire organism so as to promote metastatic tumor cell dissemination.

  • Pavlakis, E.
  • Neumann, M.
  • Stiewe, T.

Keywords

  • exosomes
  • extracellular vesicles
  • metastatic niche priming
  • mutant p53
  • p53
  • pre-metastatic niche
  • tumor microenvironment
  • of the study
  • in the collection, analyses, or interpretation of data
  • in the writing
  • of the manuscript, or in the decision to publish the results.
Publication details
DOI: 10.3390/ijms21249648
Journal: Int J Mol Sci
Number: 24
Work Type: Review
Location: UGMLC
Disease Area: LC
Partner / Member: UMR
Access-Number: 33348923

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