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| Content Provider | MDPI |
|---|---|
| Author | Maroni, Paola Bendinelli, Paola Resnati, Massimo Matteucci, Emanuela Milan, Enrico Desiderio, Maria |
| Abstract | Autophagy favours metastatic growth through fuelling energy and nutrients and resistance to anoikis, typical of disseminated-tumour cells. The autophagic process, mediated by a unique organelle, the autophagosome, which fuses with lysosomes, is divided into three steps. Several stages, especially early omegasome formation and isolation-membrane initiation, remain controversial; molecular mechanisms involve the small-GTPase Rab5a, which regulates vesicle traffic for autophagosome formation. We examined Rab5a involvement in the function of key members of ubiquitin-conjugation systems, Atg7 and LC3-lipidated, interacting with the scaffold-protein p62. Immunohistochemistry of Rab5a was performed in human specimens of bone metastasis and pair-matched breast carcinoma; the autophagic-molecular mechanisms affected by Rab5a were evaluated in human 1833 bone metastatic cells, derived from breast-carcinoma MDA-MB231 cells. To clarify the role of Rab5a, 1833 cells were transfected transiently with Rab5a-dominant negative, and/or stably with the short-hairpin RNA Atg7, were exposed to two inhibitors of autolysosome function, and LC3II and p62 expression was measured. We showed basal autophagy in bone-metastatic cells and the pivotal role of Rab5a together with Beclin 1 between the early stages, elongation of isolation membrane/closed autophagosome mediated by Atg7, and the late-degradative stages. This regulatory network might occur in bone-metastasis and in high-grade dysplastic lesions, preceding invasive-breast carcinoma and conferring phenotypic characteristics for dissemination. |
| File Size | 6879232 |
| File Format | |
| e-ISSN | 14220067 |
| DOI | 10.3390/ijms17040443 |
| Journal | International Journal of Molecular Sciences |
| Issue Number | 4 |
| Volume Number | 17 |
| Language | English |
| Publisher Date | 2016-03-25 |
| Access Restriction | Open |
| Subject Keyword | Rab5a autophagy bone metastasis |
| Content Type | Text |
| Resource Type | Article |
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