SYK is a target of lymphocyte-derived microparticles in the induction of apoptosis of human retinoblastoma cells.

Abstract

Retinoblastoma (Rb) is an aggressive childhood cancer of the developing retina. This disease is associated with epigenetic deregulation of several cancer pathways including upregulation of the proto-oncogene spleen tyrosine kinase (SYK). We have previously demonstrated that lymphocyte-derived microparticles (LMPs) possess strong cytotoxic effect on cancer cells. This report demonstrated that LMPs have potent pro-apoptotic properties on human Rb cells, which was associated with a strong reduction of SYK expression. Perturbing SYK activity in Rb cells induced cell apoptosis and upregulated expression of p53 and p21. Interestingly, inhibition of p53 or knockdown of p21, abolished LMP-induced caspase-3 activity and cell death. Blocking oxidized phospholipid-rich LMPs with a specific antibody significantly prevented LMP-induced Rb apoptosis and reversed the expression patterns of SYK, p53, p21. In summary, our results suggest that LMPs are important pro-apoptotic regulators for Rb cells through reduction of SYK expression and upregulation of the p53-p21 pathway which ultimately activates caspase-3. These data may open unexpected avenues for the development of LMPs as a novel therapeutic strategy that would be particularly useful and relevant for the treatment of Rb.

• Authors: Qian Qiu, Chun Yang, Wei Xiong, Houda Tahiri, Mathieu Payeur, Rosanne Superstein, Anne-Sophie Carret, Patrick Hamel, Benjamin Ellezam, Bussières Martin, Mark Vezina, Przemyslaw Sapieha, Guoxiang Liu, Pierre Hardy
• Journal: Apoptosis : an international journal on programmed cell death (Apoptosis) Vol. 20 Issue 12 Pg. 1613-22 (Dec 2015) ISSN: 1573-675X [Electronic] Netherlands
• PMID: 26404525 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclin-Dependent Kinase Inhibitor p21
• Intracellular Signaling Peptides and Proteins
• MAS1 protein, human
• Proto-Oncogene Mas
• Tumor Suppressor Protein p53
• Protein-Tyrosine Kinases
• SYK protein, human
• Syk Kinase
• Caspase 3

Topics

• Apoptosis (genetics)
• Caspase 3 (metabolism)
• Cell Line
• Cell Line, Tumor
• Cell-Derived Microparticles (metabolism)
• Cyclin-Dependent Kinase Inhibitor p21 (metabolism)
• Epigenesis, Genetic (genetics)
• Humans
• Intracellular Signaling Peptides and Proteins (metabolism)
• Lymphocytes (metabolism)
• Protein-Tyrosine Kinases (metabolism)
• Proto-Oncogene Mas
• Retinoblastoma (metabolism)
• Syk Kinase
• Tumor Suppressor Protein p53 (metabolism)
• Up-Regulation (genetics)