c-Abl and Arg tyrosine kinases regulate lysosomal degradation of the oncoprotein Galectin-3

Cell Death Differ. 2010 Aug;17(8):1277-87. doi: 10.1038/cdd.2010.8. Epub 2010 Feb 12.


Galectin-3 (Gal3) has important roles in tumor transformation and metastasis. This study shows that c-Abl and Abl-related gene (Arg) associate with and phosphorylate Gal3. The SH (Src homology)3 domains of c-Abl/Arg bind to a P(80)GPPSGP motif of Gal3, and Tyr79 and Tyr118 are the major tyrosine phosphorylation sites. A consequence of this interaction and phosphorylation is the significant impairment of chaperone-mediated autophagy of Gal3. Cells expressing Gal3 and treated with the c-Abl/Arg inhibitor STI571, Gal3-depleted cells, and Gal3-depleted cells expressing Gal3 phosphorylation mutants all display an increased sensitivity to apoptosis-inducing agents. In addition, tumor cells expressing the phosphorylation mutants show impaired tumorigenicity. These results partially explain the antiapoptotic effect of Abl and Arg. As tumors frequently overexpress Gal3, a c-Abl/Arg-specific inhibitor may potentially be applied along with other antitumor drugs to target the lysosomal degradation of Gal3 in tumor therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis
  • Benzamides
  • Binding Sites
  • Cell Line, Tumor
  • Galectin 3 / genetics
  • Galectin 3 / metabolism*
  • Gene Knockdown Techniques
  • Humans
  • Imatinib Mesylate
  • Lysosomes / metabolism*
  • Mice
  • Mice, Nude
  • Phosphorylation
  • Piperazines / pharmacology
  • Protein Binding
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins c-abl / antagonists & inhibitors
  • Proto-Oncogene Proteins c-abl / metabolism*
  • Pyrimidines / pharmacology
  • RNA Interference
  • Xenograft Model Antitumor Assays
  • src Homology Domains


  • Antineoplastic Agents
  • Benzamides
  • Galectin 3
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • ARG tyrosine kinase
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-abl