Galectin-3 phosphorylation is required for its anti-apoptotic function and cell cycle arrest
Tadashi Yoshii1, Tomoharu Fukumori, Yuichiro Honjo
1Tumor Progression and Metastasis Program, Karmanos Cancer Institute, Wayne State University, 110 E. Warren Ave., Detroit, MI 48201, USA.
The Journal of Biological Chemistry
|November 29, 2001
Summary
Galectin-3 phosphorylation is crucial for its anti-apoptotic function, preventing cell death and anoikis. This study shows that non-phosphorylated galectin-3 mutants lose their protective capabilities, highlighting the role of phosphorylation in cell survival signaling.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Galectin-3, a beta-galactoside-binding protein, influences cell growth, adhesion, differentiation, and tumor progression.
- Galectin-3 suppresses apoptosis and anoikis, promoting cell survival during metastasis.
- Human galectin-3 undergoes Ser(6) phosphorylation, acting as a switch for its sugar-binding ability.
Purpose of the Study:
- To investigate if galectin-3 phosphorylation is essential for its anti-apoptotic function.
- To determine the role of Ser(6) phosphorylation in galectin-3's ability to prevent cell death and anoikis.
Main Methods:
- Generated Serine to Alanine (S6A) and Serine to Glutamic Acid (S6E) mutants at the casein kinase I phosphorylation site in galectin-3.
- Transfected galectin-3 cDNAs into BT-549 breast carcinoma cells lacking endogenous galectin-3.
- Utilized metabolic labeling to assess in vivo phosphorylation and analyzed cell death, anoikis, and cell cycle regulator expression.
Main Results:
- Wild type galectin-3, but not its Ser(6) mutants, underwent phosphorylation in vivo.
- Galectin-3 mutants failed to protect cells from cisplatin-induced death and anoikis compared to wild type.
- Wild type galectin-3, upon loss of cell-substrate interaction, modulated cyclin A, cyclin D(1), p21(WAF1/CIP1), and p27(KIP1) expression.
Conclusions:
- Galectin-3 phosphorylation at Ser(6) is critical for its anti-apoptotic and anoikis-suppressing activities.
- Phosphorylation regulates galectin-3's signaling pathways involved in cell survival and cell cycle control.
- Targeting galectin-3 phosphorylation may offer therapeutic strategies for cancer metastasis.
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