| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-253 |
Sentence |
denotes |
Hyaluronan-CD44 interaction with neural Wiskott-Aldrich syndrome protein (N-WASP) promotes actin polymerization and ErbB2 activation leading to beta-catenin nuclear translocation, transcriptional up-regulation, and cell migration in ovarian tumor cells. |
| T2 |
254-510 |
Sentence |
denotes |
In this study we have investigated the interaction of hyaluronan (HA) and CD44 with the neuronal Wiskott-Aldrich syndrome protein (N-WASP) in regulating actin polymerization and ErbB2/beta-catenin signaling in human ovarian tumor cells (SK-OV-3.ipl cells). |
| T3 |
511-758 |
Sentence |
denotes |
Biochemical and immunological analyses indicate that N-WASP is expressed in SK-OV-3.ipl cells and that the binding of HA stimulates N-WASP association with CD44 and Arp2/Arp3 leading to filamentous actin formation and ovarian tumor cell migration. |
| T4 |
759-944 |
Sentence |
denotes |
In addition, HA binding promotes CD44-N-WASP association with ErbB2 and activates ErbB2 kinase activity that in turn increases phosphorylation of the cytoskeletal protein, beta-catenin. |
| T5 |
945-1090 |
Sentence |
denotes |
Subsequently, phosphorylated beta-catenin is transported into the nucleus leading to beta-catenin-mediated TCF/LEF-transcriptional co-activation. |
| T6 |
1091-1371 |
Sentence |
denotes |
Because HA-induced beta-catenin phosphorylation, nuclear translocation, and TCF/LEF transcriptional activation is effectively blocked by the ErbB2 inhibitor, AG825, we conclude that HA/CD44-N-WASP-associated ErbB2 activation is required for beta-catenin-mediated signaling events. |
| T7 |
1372-1638 |
Sentence |
denotes |
Transfection of SK-OV-3.ipl cells with N-WASP-VCA (verpolin homology, cofilin homology, and acidic domain) fragment cDNA not only blocks HA/CD44-induced N-WASP-Arp2/3 complex formation but also inhibits actin polymerization/F-actin assembly and tumor cell migration. |
| T8 |
1639-1884 |
Sentence |
denotes |
Overexpression of the N-WASP-VCA domain also significantly reduces HA-induced ErbB2 recruitment to CD44, diminishes beta-catenin phosphorylation/nuclear translocation, and abrogates TCF/LEF-specific transcriptional co-activation by beta-catenin. |
| T9 |
1885-2149 |
Sentence |
denotes |
Taken together, our findings strongly suggest that N-WASP plays a pivotal role in regulating HA-mediated CD44-ErbB2 interaction, beta-catenin signaling, and actin cytoskeleton functions that are required for tumor-specific behaviors and ovarian cancer progression. |
