TIPRL potentiates survival of lung cancer by inducing autophagy through the eIF2α-ATF4 pathway

Cited 7 time in scopus
Metadata Downloads
Title
TIPRL potentiates survival of lung cancer by inducing autophagy through the eIF2α-ATF4 pathway
Author(s)
Su Jin Jeon; Jun Ho Ahn; D Halder; Hyun Soo ChoJung Hwa Lim; Soo Young Jun; Jeong Ju LeeJi Yong Yoon; Min Hyuk Choi; Cho Rok Jung; J M Kim; Nam-Soon Kim
Bibliographic Citation
Cell Death & Disease, vol. 10, no. 12, pp. 959-959
Publication Year
2019
Abstract
Autophagy, an intracellular system of degrading damaged organelles and misfolded proteins, is essential for cancer cell survival. Despite the progress made towards understanding the mechanism, identification of novel autophagy regulators presents a major obstacle in developing anticancer therapies. Here, we examine the association between the TOR signaling pathway regulator-like (TIPRL) protein and autophagy in malignant transformation of tumors. We show that TIPRL upregulation in non-small cell lung cancer (NSCLC) potentiated autophagy activity and enabled autophagic clearance of metabolic and cellular stress, conferring a survival advantage to cancer cells. Importantly, the interaction of TIPRL with eukaryotic initiation factor 2α (eIF2α) led to eIF2α phosphorylation and activation of the eIF2α-ATF4 pathway, thereby inducing autophagy. Conversely, TIPRL depletion increased apoptosis by reducing autophagic clearance, which was markedly enhanced in TIPRL-depleted A549 xenografts treated with 2-deoxy-D-glucose. Overall, the study indicated that TIPRL is a potential regulator of autophagy and an important drug target for lung cancer therapy.
ISSN
2041-4889
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/s41419-019-2190-0
Type
Article
Appears in Collections:
Division of Research on National Challenges > Stem Cell Convergenece Research Center > 1. Journal Articles
Division of Biomedical Research > Rare Disease Research Center > 1. Journal Articles
Files in This Item:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.