The role of cbl family of ubiquitin ligases in gastric cancer exosome-induced apoptosis of Jurkat T cells

Authors

  • Jing-Lei Qu Department of Medical Oncology, The First Hospital, China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning Province, China
  • Xiu-Juan Qu Department of Medical Oncology, The First Hospital, China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning Province, China
  • Jing-Lei Qu Department of Medical Oncology, The First Hospital, China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning Province, China
  • Xiu-Juan Qu Department of Medical Oncology, The First Hospital, China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning Province, China
  • Ming-Fang Zhao Department of Medical Oncology, The First Hospital, China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning Province, China
  • Yue-E Teng Department of Medical Oncology, The First Hospital, China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning Province, China
  • Ye Zhang Department of Medical Oncology, The First Hospital, China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning Province, China
  • Ke-Zuo Hou Department of Medical Oncology, The First Hospital, China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning Province, China
  • You-Hong Jiang Institute of Cancer Research, The First Hospital, China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning Province, China
  • Xiang-Hong Yang Department of Pathology, The Shengjing Hospital, China Medical University, NO.36, Sanhao Street, Heping District, Shenyang, 110004, Liaoning Province, China
  • Yun-Peng Liu Department of Medical Oncology, The First Hospital, China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning Province, China

DOI:

https://doi.org/10.3109/02841860903032817

Abstract

Background. Exosomes are nanometer-sized vesicles with immunomodulatory functions, which are released by a diverse range of living cells. Although recent studies have shown that tumor-derived exosomes can suppress the function of T cells, the molecular mechanisms are not well understood. In the present study, we investigated the role of the Casitas B lineage lymphoma (cbl) family of ubiquitin ligases in gastric cancer exosome-induced apoptosis of Jurkat T cells. Materials and methods. By serial centrifugation and sucrose gradient ultracentrifugation, we isolated and purified the exosomes from gastric cancer SGC7901 cells, and identified them by electron microscopy and Western blotting. Cell apoptosis was detected using propidium iodide staining. Western blotting and RT-PCR was exploited to evaluate the expression of proteins and mRNA, respectively. Results. Gastric cancer exosomes induced Jurkat T cell apoptosis in a time- and dose-dependent manner and activated caspases 3, 8 and 9. The expression of Cbl-b and c-Cbl was up-regulated during exosome-induced apoptosis of cells. Meanwhile, exosomes induced ubiquitination of the p85 subunit of phosphoinositide 3-kinase (PI3K) and reduced downstream Akt activity. Inhibition of proteasome led to partial restoration of Akt activity and cell apoptosis. Discussion and Conclusions. The Cbl family of ubiquitin ligases might be involved in regulation of exosome-induced apoptosis of Jurkat T cells by increasing PI3K proteasome degradation, inactivation of PI3K/Akt signaling, thus mediating some effects of caspase activation.

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Published

2009-01-01

How to Cite

Qu, J.-L., Qu, X.-J., Qu, J.-L., Qu, X.-J., Zhao, M.-F., Teng, Y.-E., … Liu, Y.-P. (2009). The role of cbl family of ubiquitin ligases in gastric cancer exosome-induced apoptosis of Jurkat T cells. Acta Oncologica, 48(8), 1173–1180. https://doi.org/10.3109/02841860903032817

Issue

Vol. 48 No. 8 (2009): Acta Oncologica

Section

Articles