Abstract 1411: Proteogenomic analysis of the syngeneic mouse gastric stem cell-like cancer cell line
| Autor: | Hanna Yang, Hark Kyun Kim |
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| Rok vydání: | 2018 |
| Předmět: | |
| Zdroj: | Cancer Research. 78:1411-1411 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2018-1411 |
| Popis: | Gastric cancer is the third main cause of cancer deaths worldwide. To understand molecular mechanism of gastric cancer incidence and metastasis, we generated NCC-S1M lacking Smad4, Trp53 and Cdh1, which is the unique syngeneic gastric cancer cell line transplant model in the scientific society. NCC-S1M showed cancer stem cell-like features and strong tumor-initiating potential. Using proteogenomic analysis of NCC-S1M, we elucidated the specific signaling pathways that control gastric cancer stem cell-like properties and immune checkpoint. Cd274, Ccne1 and Il1rl1 were overexpressed and their protein levels were higher than normal gastric tissues. Cd274 encodes PD-L1, which is one of the important immune checkpoint proteins. The growth rate of NCC-S1M allograft was reduced after treatment with anti-PD-1. When Smad4 was ectopically expressed in NCC-S1M, Cd274 expression was decreased. In addition, TGF-β treatment induced reduction in Cd274 expression of Smad4 overexpressed NCC-S1M cells even more comparing with normal Smad4 overexpressed NCC-S1M. The knockdown of Il1rl1 in NCC-S1M reduced tumorigenicity and in vivo chemoresistance. We demonstrated that NCC-S1M focally amplified Ccne1 gene through array comparative genomic hybridization. Ccne1 knocked down NCC-S1M showed reduced metastatic potential. The proteogenomic characterization of NCC-S1M explains that Smad4 is important for PD-L1 immune evasion and that Il1rl1 has a significant role in cancer stem cell-like properties. Furthermore, it could imply that Ccne1 regulates metastasis. Citation Format: Hanna Yang, Hark Kyun Kim. Proteogenomic analysis of the syngeneic mouse gastric stem cell-like cancer cell line [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1411. |
| Databáze: | OpenAIRE |
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