| Title: |
SIDT2 RNA Transporter Promotes Lung and Gastrointestinal Tumor Development |
| Authors: |
Nguyen, TA; Bieging-Rolett, KT; Putoczki, TL; Wicks, IP; Attardi, LD; Pang, KC |
| Publisher Information: |
CELL PRESS |
| Publication Year: |
2019 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
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 KrasG12D 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 Apcmin/+ mouse model of intestinal cancer. Within the intestine, Apcmin/+;Sidt2-/- mice display accumulation of dsRNA in association with increased phosphorylation of eIF2α 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
2589-0042 |
| Relation: |
https://hdl.handle.net/11343/245009 |
| Availability: |
https://hdl.handle.net/11343/245009 |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0 ; CC BY-NC-ND |
| Accession Number: |
edsbas.D5E2E91F |
| Database: |
BASE |