Intracellular galectin-7 expression in cancer cells results from an autocrine transcriptional mechanism and endocytosis of extracellular galectin-7.
The β-galactoside binding protein galectin-7 (gal-7) is constitutively expressed at abnormally high levels in the outside milieu and intracellular compartments of many types of epithelial cancer cells, most notably in aggressive forms of ovarian and breast cancer. It is thus of utmost importance to...
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doaj-ec86febb7c77426cac14ff34df33728d2020-11-24T21:27:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-011211e018719410.1371/journal.pone.0187194Intracellular galectin-7 expression in cancer cells results from an autocrine transcriptional mechanism and endocytosis of extracellular galectin-7.Nathalie Bibens-LaulanYves St-PierreThe β-galactoside binding protein galectin-7 (gal-7) is constitutively expressed at abnormally high levels in the outside milieu and intracellular compartments of many types of epithelial cancer cells, most notably in aggressive forms of ovarian and breast cancer. It is thus of utmost importance to understand how gal-7 traffics between both intracellular and extracellular compartments to develop novel drugs that target the protumorigenic functions of galectin-7. In the present work, we report that extracellular gal-7 plays a central role in controlling intracellular gal-7 in cells. It does so via two distinct yet complementary mechanisms: firstly by increasing the transcriptional activation of lgals7 gene transcription, and secondly via re-entry into the cells. Increased mRNA levels were dose- and time-dependent and occur in all cell lines tested, including ovarian and breast cancer cell lines. Addition of recombinant gal-7 to MDA-MB-231 transfected with a luciferase reporter vector containing response elements of the lgals7 promoter indicated that increased mRNA level of lgals7 occurs via de novo gene transcription. Re-entry of extracellular gal-7 inside cells was rapid, and reached cytosolic and mitochondrial compartments. Taken together, these findings reveal the existence of a positive self-amplification pathway that regulates intracellular gal-7 expression in breast and ovarian cancer cells.http://europepmc.org/articles/PMC5678874?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nathalie Bibens-Laulan Yves St-Pierre |
spellingShingle |
Nathalie Bibens-Laulan Yves St-Pierre Intracellular galectin-7 expression in cancer cells results from an autocrine transcriptional mechanism and endocytosis of extracellular galectin-7. PLoS ONE |
author_facet |
Nathalie Bibens-Laulan Yves St-Pierre |
author_sort |
Nathalie Bibens-Laulan |
title |
Intracellular galectin-7 expression in cancer cells results from an autocrine transcriptional mechanism and endocytosis of extracellular galectin-7. |
title_short |
Intracellular galectin-7 expression in cancer cells results from an autocrine transcriptional mechanism and endocytosis of extracellular galectin-7. |
title_full |
Intracellular galectin-7 expression in cancer cells results from an autocrine transcriptional mechanism and endocytosis of extracellular galectin-7. |
title_fullStr |
Intracellular galectin-7 expression in cancer cells results from an autocrine transcriptional mechanism and endocytosis of extracellular galectin-7. |
title_full_unstemmed |
Intracellular galectin-7 expression in cancer cells results from an autocrine transcriptional mechanism and endocytosis of extracellular galectin-7. |
title_sort |
intracellular galectin-7 expression in cancer cells results from an autocrine transcriptional mechanism and endocytosis of extracellular galectin-7. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2017-01-01 |
description |
The β-galactoside binding protein galectin-7 (gal-7) is constitutively expressed at abnormally high levels in the outside milieu and intracellular compartments of many types of epithelial cancer cells, most notably in aggressive forms of ovarian and breast cancer. It is thus of utmost importance to understand how gal-7 traffics between both intracellular and extracellular compartments to develop novel drugs that target the protumorigenic functions of galectin-7. In the present work, we report that extracellular gal-7 plays a central role in controlling intracellular gal-7 in cells. It does so via two distinct yet complementary mechanisms: firstly by increasing the transcriptional activation of lgals7 gene transcription, and secondly via re-entry into the cells. Increased mRNA levels were dose- and time-dependent and occur in all cell lines tested, including ovarian and breast cancer cell lines. Addition of recombinant gal-7 to MDA-MB-231 transfected with a luciferase reporter vector containing response elements of the lgals7 promoter indicated that increased mRNA level of lgals7 occurs via de novo gene transcription. Re-entry of extracellular gal-7 inside cells was rapid, and reached cytosolic and mitochondrial compartments. Taken together, these findings reveal the existence of a positive self-amplification pathway that regulates intracellular gal-7 expression in breast and ovarian cancer cells. |
url |
http://europepmc.org/articles/PMC5678874?pdf=render |
work_keys_str_mv |
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