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 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.
Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506, United States. Electronic address: bcieply@mail.med.upenn.edu.
Benjamin
B
Cieply
Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506, United States.
Colton
C
Koontz
Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506, United States. Electronic address: sfrisch@hsc.wvu.edu.
Steven M
SM
Frisch
D023102:Anoikis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000378:metabolism*; D011485:Protein Binding; D015398:Signal Transduction
C473647:CD44S antigen; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; C101754:HAS2 protein, human; D000076002:Hyaluronan Synthases
Anoikis; Apoptosis; CD44; Epithelial-mesenchymal transition; Hyaluronan