HGAL, a lymphoma prognostic biomarker, interacts with the cytoskeleton and mediates the effects of IL-6 on cell migration

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HGAL is a newly identified germinal center (GC)-specific gene whose expression by the tumor cells correlates with a favorable prognosis in patients with diffuse large B-cell and classical Hodgkin lymphomas. The function of HGAL is unknown. Previous studies demonstrated that HGAL is dispensable for GC formation, immunoglobulin gene class-switch recombination, and somatic hypermutation. Herein, we identify a role for HGAL in the regulation of cell motility. We demonstrate that IL-6 induces the phosphorylation of the C-terminal tyrosine residue of the HGAL protein via the Lyn kinase, and promotes its relocalization from the cytoplasm to podosome-like structures. Further, IL-6-induced HGAL phosphorylation increases its interaction with myosin 11 and is associated with inhibition of cell migration. Knockdown of endogenous HGAL ameliorates IL-6-induced inhibition of cell migration, whereas overexpression of HGAL imparts inhibitory effects of IL-6 on cell migration. Taken together, our results suggest that HGAL is involved in negative regulation of lymphocyte migration, thus constraining lymphocytes to the GC. Inhibition of lymphocyte migration might contribute to the less aggressive clinical behavior of HGAL-expressing lymphomas.
Publisher
AMER SOC HEMATOLOGY
Issue Date
2007-12
Language
English
Article Type
Article
Keywords

SRC-FAMILY KINASES; GENE-EXPRESSION; B-CELLS; INTERLEUKIN-6; SURVIVAL; PROTEIN; LYN; POLYMERIZATION; CHEMOTAXIS; ACTIVATION

Citation

BLOOD, v.110, no.13, pp.4268 - 4277

ISSN
0006-4971
DOI
10.1182/blood-2007-04-087775
URI
http://hdl.handle.net/10203/88692
Appears in Collection
BS-Journal Papers(저널논문)
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