Back to Search
Start Over
TFAM is a novel mediator of immunogenic cancer cell death.
- Source :
-
OncoImmunology . 2018, Vol. 7 Issue 6, p1-1. 1p. - Publication Year :
- 2018
-
Abstract
- Immunogenic cell death (ICD) is a type of cell death that is accompanied by the release of damage-associated molecular patterns (DAMPs) and results in a dead-cell antigen-specific immune response. Here, we report that spautin-1, an inhibitor of ubiquitin-specific peptidases, triggers immunogenic cancer cell death <italic>in vitro</italic> and <italic>in vivo</italic>. The anticancer activity of spautin-1 occurs independent of autophagy inhibition, but depends on the intrinsic mitochondrial apoptosis pathway. Spautin-1 causes mitochondrial oxidative injury, which results in JUN transcription factor activation in a JNK-dependent manner. Mechanistically, activation of JUN by spautin-1 leads to apoptosis by upregulation of pro-apoptotic BAD expression. Importantly, the release of TFAM, a mitochondrial DAMP, by apoptotic cells may contribute to spautin-1-induced ICD via its action on the receptor AGER. Indeed, cancer cells treated with spautin-1 <italic>in vitro</italic> were able to elicit an anticancer immune response when inoculated <italic>in vivo</italic>, in the absence of any adjuvant. This immunogenic effect of spautin-1-treated cancer cells was lost when TFAM or AGER were neutralized by specific antibodies. Altogether, our results suggest that spautin-1 may stimulate an apoptotic pathway that results in ICD, in TFAM- and AGER-dependent fashion. [ABSTRACT FROM AUTHOR]
- Subjects :
- *CANCER cells
*CELL death
Subjects
Details
- Language :
- English
- ISSN :
- 21624011
- Volume :
- 7
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- OncoImmunology
- Publication Type :
- Academic Journal
- Accession number :
- 129593222
- Full Text :
- https://doi.org/10.1080/2162402X.2018.1431086