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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
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Nuclear export of phosphorylated galectin-3 regulates its antiapoptotic activity in response to chemotherapeutic

Yukinori Takenaka1, Tomoharu Fukumori, Tadashi Yoshii

  • 1Tumor Progression and Metastasis Program, Karmanos Cancer Institute, Detroit, Michigan 48201, USA.

Molecular and Cellular Biology
|May 4, 2004
PubMed

Insights

Galectin-3 phosphorylation at Serine 6 controls its movement from the nucleus to the cytoplasm, regulating its anti-cancer drug resistance and cell survival.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Galectin-3 (Gal-3) is implicated in cancer progression.
  • Gal-3's anti-apoptotic function is modulated by phosphorylation at Serine 6 (Ser6) by casein kinase 1 (CK1).

Purpose of the Study:

  • To investigate how Ser6 phosphorylation regulates Gal-3 function.
  • To determine the role of Gal-3 nuclear-cytoplasmic translocation in its anti-apoptotic activity.

Main Methods:

  • Generated serine-to-alanine (S6A) and serine-to-glutamic acid (S6E) Gal-3 mutants.
  • Transfected wild-type (wt) and mutant Gal-3 into BT-549 human breast carcinoma cells.
  • Treated cells with chemotherapeutic drugs and leptomycin B (nuclear export inhibitor).

Main Results:

  • Phosphorylated wt Gal-3 translocated from the nucleus to the cytoplasm upon drug treatment, protecting cells from apoptosis.
  • Non-phosphorylated Gal-3 mutants remained in the nucleus and did not confer protection.
  • Inhibiting nuclear export with leptomycin B increased drug-induced apoptosis.

Conclusions:

  • Ser6 phosphorylation acts as a molecular switch for Gal-3 translocation.
  • Cytoplasmic localization of Gal-3, triggered by phosphorylation, mediates its anti-apoptotic effects.
  • Targeting Gal-3 nuclear export could enhance cancer chemotherapy efficacy.

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