WWOX coordinates with type II TGF‐beta receptor in regulating cell‐to‐cell recognition and immune cell differentiation
Abstract
Tumor suppressor WWOX is anchored, in part, at the cell membrane/cytoskeleton area and is able to sense alterations of extracellular cues. By time‐lapse microscopy, we determined that WWOX plays an important role in controlling cell migration and cell‐to‐cell recognition. Wwox−/−MEF cells migrate individually; however, wild type Wwox+/+ MEF cells migrate collectively. When wild type Wwox+/+ MEF cells meet Wwox−/− cells, they fail to recognize each other. The knockout cells stretch out their pseudopodia to touch the wild type cells, and then move in a retrograde manner, followed by dividing immediately. The phenomenon is observed in many WWOX‐deficient cells upon encountering WWOX‐positive cells. By molecular dissection, an epitope of WWOX, namely WWgre (WWOX7–21), is responsible for attracting visiting cells. In contrast, SDRrepl (WWOX286–299) repels WWOX‐negative visiting cells. Specific antibodies against SDRrepl or WWgre block the cell‐to‐cell recognition effects. Both epitopes are physically associated with type II TGF‐beta receptor (TbetaRII). Accordingly, TGF‐beta and TbetaRII IgG antibody abolish the repellence effect. Notably, synthetic WWgre peptide is highly potent in causing T lymphocyte clonal expansion in the spleen, whereas pS14WWgre induces expansion of Hyal‐2+ CD3‐ CD19‐ (or Z) lymphocyte for memory anticancer response. Taken together, WWOX plays a crucial role in controlling cell migration, recognition, and immune cell differentiation.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2016
- Source ID
- 10.1096/fasebj.30.1_supplement.1108.9
Entities
People
- Chen‐yu Lu
- Nan‐shan Chang
- Yong‐da Sie
- Yuan Chen
Organizations
- National Cheng Kung University
- United States Department of Defense