Cytotoxic stress induces transfer of mitochondria-associated human endogenous retroviral RNA and proteins between cancer cells
| Autor: | David Diaz-Carballo, Holger Jastrow, Dirk Strumberg, P. Dammann, Mikalai Nienen, Gunther Wennemuth, Veria Khosrawipour, Camilla Wilk, Joachim Rassow, Sahitya Saka, Jacqueline Klein, Urs Giger-Pabst, Ali Haydar Acikelli |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Genetics syncytin-1/2 receptors Medizin RNA Endogeny intercellular mitochondrial transfer Mitochondrion Biology Cell biology human endogenous retroviruses (HERVs) mitochondria Cell membrane 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer cell medicine Cytotoxic T cell Epigenetics Receptor Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.21606 |
| Popis: | About 8 % of the human genome consists of human endogenous retroviruses (HERVs), which are relicts of ancient exogenous retroviral infections incurred during evolution. Although the majority of HERVs have functional gene defects or epigenetic modifications, many of them are still able to produce retroviral proteins that have been proposed to be involved in cellular transformation and cancer development. We found that, in chemo-resistant U87RETO glioblastoma cells, cytotoxic stress induced by etoposide promotes accumulation and large-scale fission of mitochondria, associated with the detection of HERV-WE1 (syncytin-1) and HERV-FRD1 (syncytin-2) in these organelles. In addition, mitochondrial preparations also contained the corresponding receptors, i.e. ASCT2 and MFSD2. We clearly demonstrated that mitochondria associated with HERV-proteins were shuttled between adjacent cancer cells not only via tunneling tubes, but also by direct cellular uptake across the cell membrane. Furthermore, anti-syncytin-1 and anti-syncytin-2 antibodies were able to specifically block this direct cellular uptake of mitochondria even more than antibodies targeting the cognate receptors. Here, we suggest that the association of mitochondria with syncytin-1/syncytin-2 together with their respective receptors could represent a novel mechanism of cell-tocell transfer. In chemotherapy-refractory cancer cells, this might open up attractive avenues to novel mitochondria-targeting therapies. OA gold |
| Databáze: | OpenAIRE |
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