Research Papers:

Binding of galectin-1 to integrin β1 potentiates drug resistance by promoting survivin expression in breast cancer cells

KeeSoo Nam, Seog-ho Son, Sunhwa Oh, Donghwan Jeon, Hyungjoo Kim, Dong-Young Noh, Sangmin Kim and Incheol Shin _

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Oncotarget. 2017; 8:35804-35823. https://doi.org/10.18632/oncotarget.16208

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KeeSoo Nam1, Seog-ho Son1, Sunhwa Oh1, Donghwan Jeon1, Hyungjoo Kim1, Dong-Young Noh2, Sangmin Kim3, Incheol Shin1,4

1Department of Life Science, Hanyang University, Seoul, 133-791, Korea

2Cancer Research Institute, Seoul National University College of Medicine, Seoul, 110-744, Korea

3Department of Surgery, Samsung Medical Center, Seoul, 135-710, Korea

4Natural Science Institute, Hanyang University, Seoul, 133-791, Korea

Correspondence to:

Incheol Shin, email: [email protected]

Keywords: galectin-1, integrin β1, STAT3, survivin, drug resistance

Received: November 25, 2016     Accepted: February 28, 2017     Published: March 15, 2017


Galectin-1 is a β-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 β1 interactions and suppression of the downstream focal adhesion kinase (FAK)/c-Src pathway. We also found that silencing of galectin-1 inhibited extracellular signal-regulated 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 knock-down 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 β1/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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