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10.3390/ijms17040443

http://scihub22266oqcxt.onion/10.3390/ijms17040443
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C4848899!4848899 !27023526
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suck abstract from ncbi


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pmid27023526
      Int+J+Mol+Sci 2016 ; 17 (4 ): 443
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  • The Autophagic Process Occurs in Human Bone Metastasis and Implicates Molecular Mechanisms Differently Affected by Rab5a in the Early and Late Stages #MMPMID27023526
  • Maroni P ; Bendinelli P ; Resnati M ; Matteucci E ; Milan E ; Desiderio MA
  • Int J Mol Sci 2016[Mar]; 17 (4 ): 443 PMID27023526 show ga
  • 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.
  • |Autophagy [MESH]
  • |Autophagy-Related Protein 7/antagonists & inhibitors/genetics/metabolism [MESH]
  • |Beclin-1/genetics/metabolism [MESH]
  • |Blotting, Western [MESH]
  • |Bone Neoplasms/metabolism/*pathology/secondary [MESH]
  • |Breast Neoplasms/metabolism/*pathology [MESH]
  • |Cell Line, Tumor [MESH]
  • |Female [MESH]
  • |Humans [MESH]
  • |Immunohistochemistry [MESH]
  • |Microscopy, Fluorescence [MESH]
  • |Microtubule-Associated Proteins/metabolism [MESH]
  • |Neoplasm Staging [MESH]
  • |RNA Interference [MESH]
  • |RNA, Small Interfering/metabolism [MESH]
  • |RNA-Binding Proteins/metabolism [MESH]


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