Cancer Cells Shuttle Extracellular Vesicles Containing Oncogenic Mutant p53 Proteins to the Tumor Microenvironment
The Shraga Segal Department of Microbiology, Immunology and Genetics, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
Division of Cellular & Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore, Singapore 169610, Singapore
p53 Laboratory (p53Lab), Agency for Science, Technology, and Research (A*STAR), Singapore 138648, Singapore
Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore 169857, Singapore
Author to whom correspondence should be addressed.
Academic Editor: Elaine Dunlop
Received: 2 May 2021
Revised: 9 June 2021
Accepted: 11 June 2021
Published: 15 June 2021
In addition to the classical cell-to-cell communication patterns, extracellular vesicles (EVs) are instrumental in conveying molecular messages across cell types and have the potential to mediate changes at a tissue level. Since it is now appreciated that carcinomas are fundamentally reliant on two-way communication with activated cells in the tumor microenvironment, elucidating the roles of EVs exchange and of the cargo that is transferred is essential to obtain a thorough understanding of tumor progression. This study reveals that mutant p53 proteins—the result of the most frequent mutated gene in human cancer—are packed into EVs and delivered to neighboring cells with the potential to reprogram immune cells and subsequently establish a positive feedback loop that will enhance tumor progression. This non-cell autonomous role of mutant p53 is evidence of an extra layer of communication that is orchestrated by smaller vesicles that transfer oncogenic elements between cellular entities. Building on the foundation of our work on mutant p53, future studies may aim to characterize the potential activation of additional oncogenes, thus opening new paths of research at the interface of extracellular vesicles, cancer, and evolution.