Abstract：
:The lipid hydrolase enzyme acid sphingomyelinase (ASM) is required for the conversion of the lipid cell membrane component sphingomyelin into ceramide. In cancer cells, ASM-mediated ceramide production is important for apoptosis, cell proliferation, and immune modulation, highlighting ASM as a potential multimodal therapeutic target. In this study, we demonstrate elevated ASM activity in the lung tumor environment and blood serum of patients with non-small cell lung cancer (NSCLC). RNAi-mediated attenuation of SMPD1 in human NSCLC cells rendered them resistant to serum starvation-induced apoptosis. In a murine model of lung adenocarcinoma, ASM deficiency reduced tumor development in a manner associated with significant enhancement of Th1-mediated and cytotoxic T-cell-mediated antitumor immunity. Our findings indicate that targeting ASM in NSCLC can act by tumor cell-intrinsic and -extrinsic mechanisms to suppress tumor cell growth, most notably by enabling an effective antitumor immune response by the host. Cancer Res; 77(21); 5963-76. ©2017 AACR.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Kachler K,Bailer M,Heim L,Schumacher F,Reichel M,Holzinger CD,Trump S,Mittler S,Monti J,Trufa DI,Rieker RJ,Hartmann A,Sirbu H,Kleuser B,Kornhuber J,Finotto Sdoi
10.1158/0008-5472.CAN-16-3313subject
Has Abstractpub_date
2017-11-01 00:00:00pages
5963-5976issue
21eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-16-3313journal_volume
77pub_type
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