IGFBP-3 blocks hyaluronan-CD44 signaling, leading to increased acetylcholinesterase levels in A549 cell media and apoptosis in a p53-dependent manner

<p>Insulin-like growth factor binding protein-3 (IGFBP-3) belongs to a family of six IGF binding proteins. We previously found that IGFBP-3 exerts its cytotoxic effects on A549 (p53 wild-type) cell survival through a mechanism that depends on hyaluronan-CD44 interactions. To shed light on the mechanism employed, we used CD44-negative normal human lung cells (HFL1), A549, and H1299 (p53-null) lung cancer cells. A synthetic IGFBP-3 peptide (²¹⁵-KKGFYKKKQCRPSKGRKR-²³²) but not the mutant (K228AR230A), was able to bind hyaluronan more efficiently than the analogous sequences from the other IGFBPs. In a manner comparable to that of the IGFBP-3 protein, the peptide blocked HA-CD44 signaling, and more effectively inhibited viability of A549 cells than viability of either H1299 or HFL1 cell lines. Treatment with the IGFBP-3 protein or its peptide, resulted in increased acetylcholinesterase concentration and activity in the A549 cell media but not in the media of either HFL1 or H1299, an effect that correlated with increased apoptosis and decreased cell viability. These effects were diminished upon the same treatment of A549 cells transfected with either p53 siRNA or acetylcholinesterase siRNA. Taken together, our results show that IGFBP-3 or its peptide blocks hyaluronan-CD44 signaling via a mechanism that depends on both p53 and acetylcholinesterase.</p>

Name thesis:degree_name

Master of Science (MS)

Level thesis:degree_level

Campus Only Thesis

Discipline thesis:degree_discipline

Biology

Year dc:date.available

2021

Author dc:creator

• Price, Deanna

Contributors dc:contributor

• Hedeel Evans, Ph.D., Advisor
• Michael Angell, Ph.D.
• Aaron Liepman, Ph.D.

• Cell and Developmental Biology

Repository record dc:identifier

https://commons.emich.edu/theses/1059

OAI identifier oai:identifier

oai:commons.emich.edu:theses-2436