Document Detail


Secretion of novel SEL1L endogenous variants is promoted by ER stress/UPR via endosomes and shed vesicles in human cancer cells.
MedLine Citation:
PMID:  21359144     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We describe here two novel endogenous variants of the human endoplasmic reticulum (ER) cargo receptor SEL1LA, designated p38 and p28. Biochemical and RNA interference studies in tumorigenic and non-tumorigenic cells indicate that p38 and p28 are N-terminal, ER-anchorless and more stable relative to the canonical transmembrane SEL1LA. P38 is expressed and constitutively secreted, with increase after ER stress, in the KMS11 myeloma line and in the breast cancer lines MCF7 and SKBr3, but not in the non-tumorigenic breast epithelial MCF10A line. P28 is detected only in the poorly differentiated SKBr3 cell line, where it is secreted after ER stress. Consistently with the presence of p38 and p28 in culture media, morphological studies of SKBr3 and KMS11 cells detect N-terminal SEL1L immunolabeling in secretory/degradative compartments and extracellularly-released membrane vesicles. Our findings suggest that the two new SEL1L variants are engaged in endosomal trafficking and secretion via vesicles, which could contribute to relieve ER stress in tumorigenic cells. P38 and p28 could therefore be relevant as diagnostic markers and/or therapeutic targets in cancer.
Authors:
Monica Cattaneo; Lavinia Vittoria Lotti; Simone Martino; Massimo Alessio; Antonio Conti; Angela Bachi; Renato Mariani-Costantini; Ida Biunno
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-02-17
Journal Detail:
Title:  PloS one     Volume:  6     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2011  
Date Detail:
Created Date:  2011-03-01     Completed Date:  2011-09-01     Revised Date:  2013-03-28    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e17206     Citation Subset:  IM    
Affiliation:
Institute for Biomedical Technologies, National Research Council, Milan, Italy.
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MeSH Terms
Descriptor/Qualifier:
Cell Line, Tumor
Cells, Cultured
Endoplasmic Reticulum / metabolism*
Endosomes / metabolism*,  physiology
HeLa Cells
Humans
Neoplasms / genetics,  metabolism*,  pathology
Protein Isoforms / genetics,  secretion
Protein Transport / physiology
Proteins / genetics,  secretion*
Secretory Vesicles / metabolism*,  pathology
Stress, Physiological / physiology
Tumor Markers, Biological / genetics,  secretion
Unfolded Protein Response / physiology*
Chemical
Reg. No./Substance:
0/Protein Isoforms; 0/Proteins; 0/SEL1L protein, human; 0/Tumor Markers, Biological
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