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Binding of galectin-1 to integrin beta 1 potentiates drug resistance by promoting survivin expression in breast cancer cells

Title
Binding of galectin-1 to integrin beta 1 potentiates drug resistance by promoting survivin expression in breast cancer cells
Author
신인철
Keywords
galectin-1; integrin beta 1; STAT3; survivin; drug resistance
Issue Date
2017-05
Publisher
IMPACT JOURNALS LLC
Citation
ONCOTARGET, v. 8, no. 22, page. 35804-35823
Abstract
Galectin-1 is a beta-galactoside binding protein secreted by many types of aggressive cancer cells. Although many studies have focused on the role of galectin-1 in cancer progression, relatively little attention has been paid to galectin-1 as an extracellular therapeutic target. To elucidate the molecular mechanisms underlying galectin-1-mediated cancer progression, we established galectin-1 knock-down cells via retroviral delivery of short hairpin RNA (shRNA) against galectin-1 in two triple-negative breast cancer (TNBC) cell lines, MDA-MB-231 and Hs578T. Ablation of galectin-1 expression decreased cell proliferation, migration, invasion, and doxorubicin resistance. We found that these effects were caused by decreased galectin-1-integrin 1 interactions and suppression of the downstream focal adhesion kinase (FAK)/cSrc pathway. We also found that silencing of galectin-1 inhibited extracellular signalregulated kinase (ERK)/signal transducer and activator of transcription 3 (STAT3) signaling, thereby down-regulating survivin expression. This finding implicates STAT3 as a transcription factor for survivin. Finally, rescue of endogenous galectin-1 knockdown and recombinant galectin-1 treatment both recovered signaling through the FAK/c-Src/ERK/STAT3/survivin pathway. Taken together, these results suggest that extracellular galectin-1 contributes to cancer progression and doxorubicin resistance in TNBC cells. These effects appear to be mediated by galectin-1-induced up-regulation of the integrin beta 1/FAK/c-Src/ERK/STAT3/survivin pathway. Our results imply that extracellular galectin-1 has potential as a therapeutic target for triple-negative breast cancer.
URI
http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=16208&path[]=51849http://repository.hanyang.ac.kr/handle/20.500.11754/113935
ISSN
1949-2553
DOI
10.18632/oncotarget.16208
Appears in Collections:
COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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