Binding of galectin-1 to integrin β1 potentiates drug resistance by promoting survivin expression in breast cancer cellsopen access
- Authors
- Nam, KeeSoo; Son, Seog-Ho; Oh, Sunhwa; Jeon, Donghwan; Kim, Hyungjoo; Noh, Dong-Young; Kim, Sangmin; Shin, Incheol
- Issue Date
- May-2017
- Publisher
- IMPACT JOURNALS LLC
- Keywords
- galectin-1; integrin beta 1; STAT3; survivin; drug resistance
- Citation
- ONCOTARGET, v.8, no.22, pp.35804 - 35823
- Indexed
- SCIE
SCOPUS
- Journal Title
- ONCOTARGET
- Volume
- 8
- Number
- 22
- Start Page
- 35804
- End Page
- 35823
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/20361
- DOI
- 10.18632/oncotarget.16208
- 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.
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