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The membrane molecule RCAS1 induces immune cell apoptosis via the RCAS1-RCAS1R pathway
Yuanyuan Zhang1, Jie Zhu, Xuejun Hong
1The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China. zhang_y_y@sohu.com
Abstract:
Tumor-associated antigen receptor-binding cancer antigen expressed on SiSo cells (RCAS1) has been identified as an estrogen-responsive gene and reportedly acts as a ligand for a putative receptor present in a variety of human cell lines and peripheral lymphocytes, thus leading them to apoptosis. In this study, we investigated the biological function of RCAS1 in vitro in inducing the apoptosis of immune cells. We detected the expression of the RCAS1 receptor (RCAS1R) in the cell lines, and investigated the mechanisms behind the apoptosis induced by RCAS1. HeLa cells were transfected with recombinant adenovirus Ad-RCAS1. RCAS1 induced the apoptosis of activated T cells, K562 cells and phytohemagglutinin (PHA)-activated Jurkat cells via the RCAS1-RCAS1R pathway. The expression of RCAS1R was induced. The intracellular overexpression of RCAS1 inhibited the growth of Jurkat and K562 cells. The expression of RCAS1 negatively correlated with the expression of glycogen synthase kinase 3β (GSK3β), but positively correlated with the expression of phosphorylated GSK3β (phGSK3β). RCAS1 expression was identified as a brown staining pattern in the breast cancer specimens. These findings may provide insight into the mechanisms through which tumor cells escape from immune surveillance.
Insights
Tumor-associated antigen RCAS1 induces immune cell apoptosis via the RCAS1-RCAS1R pathway. This mechanism, involving GSK3β, may explain how cancer cells evade immune surveillance.
Area of Science:
- Immunology
- Molecular Biology
- Cancer Research
Background:
- Tumor-associated antigen receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is an estrogen-responsive gene.
- RCAS1 acts as a ligand, inducing apoptosis in various human cell lines and lymphocytes via a putative receptor.
- Understanding RCAS1's role in immune cell apoptosis is crucial for cancer immune evasion mechanisms.
Purpose of the Study:
- To investigate the in vitro biological function of RCAS1 in inducing immune cell apoptosis.
- To detect the expression of the RCAS1 receptor (RCAS1R) and elucidate the mechanisms of RCAS1-induced apoptosis.
- To explore the correlation between RCAS1 expression and GSK3β signaling in cancer.
Main Methods:
- HeLa cells were transfected with recombinant adenovirus Ad-RCAS1.
- RCAS1-induced apoptosis was assessed in activated T cells, K562 cells, and PHA-activated Jurkat cells.
- Expression of RCAS1R, GSK3β, and phosphorylated GSK3β (phGSK3β) was analyzed. Breast cancer specimens were examined for RCAS1 expression patterns.
Main Results:
- RCAS1 induced apoptosis in activated T cells, K562 cells, and Jurkat cells through the RCAS1-RCAS1R pathway.
- RCAS1R expression was induced, and intracellular RCAS1 overexpression inhibited Jurkat and K562 cell growth.
- RCAS1 expression negatively correlated with GSK3β and positively correlated with phGSK3β. Brown staining for RCAS1 was observed in breast cancer specimens.
Conclusions:
- RCAS1 induces immune cell apoptosis via the RCAS1-RCAS1R pathway, potentially contributing to tumor immune evasion.
- The study elucidates the molecular mechanisms of RCAS1-mediated apoptosis and its signaling pathways.
- RCAS1 expression in breast cancer suggests its role in tumor progression and immune escape strategies.
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