期刊
BIOMOLECULES
卷 10, 期 2, 页码 -出版社
MDPI
DOI: 10.3390/biom10020307
关键词
p53; tumor suppressor; secretome; extracellular vesicles; exosomes; tumor microenvironment; pre-metastatic niches; metastasis
资金
- Deutsche Forschungsgemeinschaft [STI 182/7-1, STI 182/13-1, TRR81 TPA10, GRK 2573/1]
- Deutsche Krebshilfe [70112623]
- Deutsche Jose Carreras Leukamie Stiftung [09 R/2018]
- German Center for Lung Research (DZL)
- von Behring-Rontgen Stiftung [65-0004, 66-LV06]
p53 suppresses tumorigenesis by activating a plethora of effector pathways. While most of these operate primarily inside of cells to limit proliferation and survival of incipient cancer cells, many extend to the extracellular space. In particular, p53 controls expression and secretion of numerous extracellular factors that are either soluble or contained within extracellular vesicles such as exosomes. As part of the cellular secretome, they execute key roles in cell-cell communication and extracellular matrix remodeling. Mutations in the p53-encoding TP53 gene are the most frequent genetic alterations in cancer cells, and therefore, have profound impact on the composition of the tumor cell secretome. In this review, we discuss how the loss or dominant-negative inhibition of wild-type p53 in concert with a gain of neomorphic properties observed for many mutant p53 proteins, shapes a tumor cell secretome that creates a supportive microenvironment at the primary tumor site and primes niches in distant organs for future metastatic colonization.
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