SIDT2 RNA transporter promotes lung and gastrointestinal tumor development
- Author(s)
- Nguyen, TA; Bieging-Rolett, KT; Putoczki, TL; Wicks, IP; Attardi, LD; Pang, KC;
- Journal Title
- iScience
- Publication Type
- Journal Article
- Abstract
- RNautophagy is a newly described type of selective autophagy whereby cellular RNAs are transported into lysosomes for degradation. This process involves the transmembrane protein SIDT2, which transports double-stranded RNA (dsRNA) across the endolysosomal membrane. We previously demonstrated that SIDT2 is a transcriptional target of p53, but its role in tumorigenesis, if any, is unclear. Unexpectedly, we show here that Sidt2(-/-) mice with concurrent oncogenic Kras(G12D) activation develop significantly fewer tumors than littermate controls in a mouse model of lung adenocarcinoma. Consistent with this observation, loss of SIDT2 also leads to enhanced survival and delayed tumor development in an Apc(min/+) mouse model of intestinal cancer. Within the intestine, Apc(min/+);Sidt2(-/-) mice display accumulation of dsRNA in association with increased phosphorylation of eIF2alpha and JNK as well as elevated rates of apoptosis. Taken together, our data demonstrate a role for SIDT2, and by extension RNautophagy, in promoting tumor development.
- Publisher
- Elsevier
- Research Division(s)
- Inflammation; Personalised Oncology
- PubMed ID
- 31546103
- Publisher's Version
- https://doi.org/10.1016/j.isci.2019.09.009
- Open Access at Publisher's Site
https://doi.org/10.1016/j.isci.2019.09.009- NHMRC Grants
- NHMRC/1064591,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2019-10-23 02:22:53
Last Modified: 2019-10-23 02:42:46