Cell aggregation induces phosphorylation of PECAM-1 and Pyk2 and promotes tumor cell anchorage-independent growth.
BACKGROUND
Apoptosis caused by inadequate or inappropriate cell-matrix interactions is defined as anoikis. Although transformed cells are known to be anoikis-resistant, the underlying mechanisms have not been well understood. We investigated the mechanisms of anoikis resistance of tumor cells.


RESULTS
We observed that cell aggregation in suspension promoted cell survival and proliferation. We demonstrated a correlation between tumor cell aggregation in suspension and cell growth in soft agar. Analysis of tyrosine kinase-mediated cell survival and growth signaling pathways revealed increased levels of tyrosine-phosphorylation of PECAM-1 and Pyk2 in cell aggregates. We also showed that PECAM-1 and Pyk2 physically interact with each other, and that PECAM-1 carrying a deletion of exons 11-16 could no longer bind to Pyk2. Furthermore, RNA interference-mediated reduction of Pyk2 and PECAM-1 protein levels reduced cell aggregation and inhibited the growth of tumor cells in soft agar.


CONCLUSIONS
The data demonstrated that Pyk2 and PECAM-1 were critical mediators of both anchorage-independent growth and anoikis resistance in tumor cells.
Zhang
Xing
X
Department of Pharmacology, Shanghai Institute of Materia Medica, China Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China. xingzhangg@hotmail.com
Xu
Li-hua
LH
Yu
Qiang
Q
D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion; D002449:Cell Aggregation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D003114:Colony-Forming Units Assay; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D011485:Protein Binding; D015398:Signal Transduction
D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019000:Phosphotyrosine; D051418:Focal Adhesion Kinase 2