CD44S-hyaluronan interactions protect cells resulting from EMT against anoikis

The detachment of normal epithelial cells from matrix triggers an apoptotic response known as anoikis, during homeostatic turnover. Metastatic tumor cells evade anoikis, by mechanisms that are only partly characterized. In particular, the epithelial–mesenchymal transition (EMT) in a subset of invasi...

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Bibliographic Details
Published in:Matrix biology 2015-10, Vol.48, p.55-65
Main Authors: Cieply, Benjamin, Koontz, Colton, Frisch, Steven M.
Format: Article
Language:English
Subjects:
Anoikis
Anoikis - genetics
Apoptosis
CD44
Cell Line, Tumor
Cell Proliferation
Epithelial Cells - metabolism
Epithelial Cells - pathology
Epithelial-Mesenchymal Transition
Extracellular Matrix - chemistry
Extracellular Matrix - metabolism
Gene Expression Regulation, Neoplastic
Glucuronosyltransferase - genetics
Glucuronosyltransferase - metabolism
Humans
Hyaluronan
Hyaluronan Receptors - genetics
Hyaluronan Receptors - metabolism
Hyaluronan Synthases
Hyaluronic Acid - metabolism
Protein Binding
Signal Transduction
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Summary:The detachment of normal epithelial cells from matrix triggers an apoptotic response known as anoikis, during homeostatic turnover. Metastatic tumor cells evade anoikis, by mechanisms that are only partly characterized. In particular, the epithelial–mesenchymal transition (EMT) in a subset of invasive tumor cells confers anoikis-resistance. In some cases, EMT up-regulates the cancer stem cell marker CD44S and the enzyme hyaluronic acid synthase-2 (HAS2). CD44S is the major receptor for hyaluronan in the extracellular matrix. Herein, we demonstrate that CD44S, unlike the CD44E isoform expressed in normal epithelial cells, contributes to the protection against anoikis. This protection requires the interaction of CD44S with hyaluronan (HA). CD44S–HA interaction is proposed to play an important role in tumor metastasis through enhanced cell survival under detached conditions.
ISSN:0945-053X
1569-1802
DOI:10.1016/j.matbio.2015.04.010