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 bei...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/24/9648 |
| _version_ | 1797544314123845632 |
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| author | Evangelos Pavlakis Michelle Neumann Thorsten Stiewe |
| author_facet | Evangelos Pavlakis Michelle Neumann Thorsten Stiewe |
| author_sort | Evangelos Pavlakis |
| collection | DOAJ |
| description | 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 <i>Tumor protein p53</i> (<i>TP53</i>) 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. |
| first_indexed | 2024-03-10T13:58:41Z |
| format | Article |
| id | doaj.art-fabebf17031f4343ac7913f1aef030fe |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T13:58:41Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-fabebf17031f4343ac7913f1aef030fe2023-11-21T01:23:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-012124964810.3390/ijms21249648Extracellular Vesicles: Messengers of p53 in Tumor–Stroma Communication and Cancer MetastasisEvangelos Pavlakis0Michelle Neumann1Thorsten Stiewe2Institute of Molecular Oncology, Philipps University, 35034 Marburg, GermanyInstitute of Molecular Oncology, Philipps University, 35034 Marburg, GermanyInstitute of Molecular Oncology, Philipps University, 35034 Marburg, GermanyTumor 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 <i>Tumor protein p53</i> (<i>TP53</i>) 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.https://www.mdpi.com/1422-0067/21/24/9648extracellular vesiclesexosomesp53mutant p53tumor microenvironmentmetastatic niche priming |
| spellingShingle | Evangelos Pavlakis Michelle Neumann Thorsten Stiewe Extracellular Vesicles: Messengers of p53 in Tumor–Stroma Communication and Cancer Metastasis International Journal of Molecular Sciences extracellular vesicles exosomes p53 mutant p53 tumor microenvironment metastatic niche priming |
| title | Extracellular Vesicles: Messengers of p53 in Tumor–Stroma Communication and Cancer Metastasis |
| title_full | Extracellular Vesicles: Messengers of p53 in Tumor–Stroma Communication and Cancer Metastasis |
| title_fullStr | Extracellular Vesicles: Messengers of p53 in Tumor–Stroma Communication and Cancer Metastasis |
| title_full_unstemmed | Extracellular Vesicles: Messengers of p53 in Tumor–Stroma Communication and Cancer Metastasis |
| title_short | Extracellular Vesicles: Messengers of p53 in Tumor–Stroma Communication and Cancer Metastasis |
| title_sort | extracellular vesicles messengers of p53 in tumor stroma communication and cancer metastasis |
| topic | extracellular vesicles exosomes p53 mutant p53 tumor microenvironment metastatic niche priming |
| url | https://www.mdpi.com/1422-0067/21/24/9648 |
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