Proteogenomic analysis of NCC-S1M, a gastric cancer stem cell-like cell line that responds to anti-PD-1.
To elucidate signaling pathways that regulate gastric cancer stem cell (CSC) phenotypes and immune checkpoint, we performed a proteogenomic analysis of NCC-S1M, which is a gastric cancer cell line with CSC-like characteristics and is the only syngeneic gastric tumor cell line transplant model created in the scientific community. We found that the NCC-S1M allograft was responsive to anti-PD-1 treatment, and overexpressed Cd274 encoding PD-L1. PD-L1 was transcriptionally activated by loss of the TGF-β signaling. Il1rl1 protein was overexpressed in NCC-S1M cells compared with NCC-S1 cells that are less tumorigenic and less chemoresistant. Il1rl1 knockdown in NCC-S1M cells reduced tumorigenic potential and in vivo chemoresistance. Our proteogenomic analysis demonstrates a role of Smad4 loss in the PD-L1 immune evasion, as well as Il1rl1's role in CSC-like properties of NCC-S1M.
National Cancer Center, 323 Ilsanro, Goyang, Gyeonggi 10408, Republic of Korea; College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea.
Jun Won
JW
Park
National Cancer Center, 323 Ilsanro, Goyang, Gyeonggi 10408, Republic of Korea.
Hyejin
H
Um
National Cancer Center, 323 Ilsanro, Goyang, Gyeonggi 10408, Republic of Korea.
Hanna
H
Yang
National Cancer Center, 323 Ilsanro, Goyang, Gyeonggi 10408, Republic of Korea.
Woori
W
Ko
College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea.
Dae-Yong
DY
Kim
National Cancer Center, 323 Ilsanro, Goyang, Gyeonggi 10408, Republic of Korea. Electronic address: hkim@ncc.re.kr.
Hark Kyun
HK
Kim
D000818:Animals; D000970:Antineoplastic Agents; D063646:Carcinogenesis / Q000187:drug effects / Q000276:immunology; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D051379:Mice; D009363:Neoplasm Proteins / Q000276:immunology*; D014411:Neoplastic Stem Cells / Q000145:classification / Q000187:drug effects* / Q000276:immunology*; D020543:Proteome / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013274:Stomach Neoplasms / Q000145:classification / Q000188:drug therapy* / Q000276:immunology*
D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D020543:Proteome
Cancer; Ccne1; Gastric; Il1rl1; PD-L1