Abstract |
Both high and low molecular weight hyaluronan (HMW-HA vs. LMW-HA) exist in various tissues and cells. In this study, we investigated LMW-HA-mediated CD44 interaction with Toll-like receptors (TLRs), the actin filament-associated protein (AFAP-110), and a myeloid differentiation factor (MyD88) in breast tumor cells (MDA-MB-231 cells). Our data indicate that LMW-HA (but not HMW-HA) preferentially stimulates a physical association between CD44 and TLRs followed by a concomitant recruitment of AFAP-110 and MyD88 into receptor-containing complexes in breast tumor cells. LMW-HA-activated AFAP-110 then binds to filamentous actin ( F-actin) resulting in MyD88/nuclear factor-κB (NF-κB) nuclear translocation, NF-κB-specific transcription, and target gene [interleukine 1β and interleukine-8 (IL-1β and IL-8)] expression. These signaling events lead to proinflammatory cytokine/ chemokine production in the breast tumor cells. AFAP-110-F-actin (activated by LMW-HA) also promotes tumor cell invasion. Downregulation of AFAP-110 or MyD88 by transfecting breast tumor cells with AFAP-110 siRNA or MyD88 siRNA, respectively not only blocks the ability of LMW-HA to stimulate AFAP-110-actin function, but also impairs MyD88-NF-κB nuclear translocation and NF-κB transcriptional activation. Consequently, both IL-1β/IL-8 production and tumor cell invasion are impaired. Taken together, these findings suggest that LMW-HA plays an important role in CD44-TLR-associated AFAP-110-actin interaction and MyD88-NF-κB signaling required for tumor cell behaviors, which may contribute to the progression of breast cancer.
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Authors | Lilly Y W Bourguignon, Gabriel Wong, Christine A Earle, Weiliang Xia |
Journal | Cytoskeleton (Hoboken, N.J.)
(Cytoskeleton (Hoboken))
Vol. 68
Issue 12
Pg. 671-93
(Dec 2011)
ISSN: 1949-3592 [Electronic] United States |
PMID | 22031535
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Copyright | Copyright © 2011 Wiley Periodicals, Inc. |
Chemical References |
- AFAP 110
- Chemokines
- Cytokines
- Hyaluronan Receptors
- Microfilament Proteins
- NF-kappa B
- Phosphoproteins
- RNA, Small Interfering
- Hyaluronic Acid
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Topics |
- Animals
- Breast Neoplasms
(drug therapy, genetics, metabolism, pathology)
- Cell Line, Tumor
- Cell Movement
(physiology)
- Chemokines
(biosynthesis, genetics, metabolism)
- Cytokines
(biosynthesis, genetics, metabolism)
- Female
- Humans
- Hyaluronan Receptors
(genetics, metabolism)
- Hyaluronic Acid
(pharmacology)
- Microfilament Proteins
(genetics, metabolism)
- NF-kappa B
(biosynthesis, genetics, metabolism)
- Phosphoproteins
(genetics, metabolism)
- RNA, Small Interfering
(genetics, metabolism)
- Rats
- Signal Transduction
- Transfection
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