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

Evangelos PavlakisMichelle NeumannThorsten Stiewe
Published in: International journal of molecular sciences (2020)
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.
Keyphrases
  • squamous cell carcinoma
  • wild type
  • stem cells
  • gene expression
  • poor prognosis
  • case report
  • mesenchymal stem cells
  • lymph node
  • long non coding rna
  • young adults
  • nucleic acid