Cytotoxic stress induces transfer of mitochondria-associated human endogenous retroviral RNA and proteins between cancer cells

摘要: About 8 % of the human genome consists endogenous retroviruses (HERVs), which are relicts ancient exogenous retroviral infections incurred during evolution. Although majority HERVs have functional gene defects or epigenetic modifications, many them still able to produce proteins that been proposed be involved in cellular transformation and cancer development. We found that, chemo-resistant U87RETO glioblastoma cells, cytotoxic stress induced by etoposide promotes accumulation large-scale fission mitochondria, associated with detection HERV-WE1 (syncytin-1) HERV-FRD1 (syncytin-2) these organelles. In addition, mitochondrial preparations also contained corresponding receptors, i.e. ASCT2 MFSD2. clearly demonstrated mitochondria HERV-proteins were shuttled between adjacent cells not only via tunneling tubes, but direct uptake across cell membrane. Furthermore, anti-syncytin-1 anti-syncytin-2 antibodies specifically block this even more than targeting cognate receptors. Here, we suggest association syncytin-1/syncytin-2 together their respective receptors could represent a novel mechanism cell-to-cell transfer. chemotherapy-refractory might open up attractive avenues mitochondria-targeting therapies.