TRIB3-EGFR interaction promotes lung cancer progression and defines a therapeutic target.

Nature Communications
Jiao-Jiao YuZhuo-Wei Hu

Abstract

High expression or aberrant activation of epidermal growth factor receptor (EGFR) is related to tumor progression and therapy resistance across cancer types, including non-small cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitors (TKIs) are first-line therapy for NSCLC. However, patients eventually deteriorate after inevitable acquisition of EGFR TKI-resistant mutations, highlighting the need for therapeutics with alternative mechanisms of action. Here, we report that the elevated tribbles pseudokinase 3 (TRIB3) is positively associated with EGFR stability and NSCLC progression. TRIB3 interacts with EGFR and recruits PKCα to induce a Thr654 phosphorylation and WWP1-induced Lys689 ubiquitination in the EGFR juxtamembrane region, which enhances EGFR recycling, stability, downstream activity, and NSCLC stemness. Disturbing the TRIB3-EGFR interaction with a stapled peptide attenuates NSCLC progression by accelerating EGFR degradation and sensitizes NSCLC cells to chemotherapeutic agents. These findings indicate that targeting EGFR degradation is a previously unappreciated therapeutic option in EGFR-related NSCLC.

References

Apr 21, 2005·The Journal of Biological Chemistry·Kiattawee ChoowongkomonFrank D Sönnichsen
Mar 14, 2008·The New England Journal of Medicine·Fortunato Ciardiello, Giampaolo Tortora
Oct 27, 2009·Molecular Cell·Chunaram ChoudharyHubert Serve
Jul 24, 2010·British Journal of Pharmacology·Carol KilkennyUNKNOWN NC3Rs Reporting Guidelines Working Group
Jun 3, 2011·The Journal of Clinical Investigation·Lauren L C MarottaKornelia Polyak
Jun 7, 2011·Nature Cell Biology·Carine JoffreStéphanie Kermorgant
Jul 14, 2011·Neoplasia : an International Journal for Oncology Research·Dipankar RayMukesh K Nyati
Nov 5, 2011·Cellular and Molecular Life Sciences : CMLS·Xu Zhi, Ceshi Chen
May 12, 2012·Endocrine Reviews·Sabrina PrudenteVincenzo Trischitta
May 25, 2012·Nature Reviews. Cancer·Jessica B Casaletto, Andrea I McClatchey
Jul 4, 2012·Nature Genetics·Zhenfeng ZhangTrever G Bivona
Oct 23, 2012·Biochimica Et Biophysica Acta·Bhopal MohapatraHamid Band
Mar 9, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Helena A YuGregory J Riely
Mar 29, 2013·Molecular Cancer Research : MCR·Hideki TeraiTomoko Betsuyaku
Apr 6, 2013·The International Journal of Biological Markers·Marloes WennemersPaul N Span
Jul 16, 2013·International Journal of Cancer. Journal International Du Cancer·Ke LiZhuo-Wei Hu
Aug 16, 2013·Proceedings of the National Academy of Sciences of the United States of America·Yong S ChangTomi K Sawyer
Oct 9, 2014·The Journal of Clinical Investigation·Hye-Young ParkChang-Woo Lee
Nov 18, 2014·Nature Communications·Edward R BallisterDavid M Chenoweth
Nov 21, 2014·Current Drug Targets·Fiona H TanRodney B Luwor
Apr 18, 2015·Nucleic Acids Research·Jianyi Yang, Yang Zhang
Apr 30, 2015·The New England Journal of Medicine·Lecia V SequistD Ross Camidge
Dec 17, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Tatiana ErazoJose M Lizcano
Jan 23, 2016·Cancer Letters·Lauren MacDonaghMartin P Barr
Feb 2, 2016·Trends in Cell Biology·Xiaojun TanRichard A Anderson
Feb 9, 2016·Biochimie·Debasis MondalPartha K Chandra
Feb 24, 2016·Pharmacology & Therapeutics·Jihe Zhao

❮ Previous
Next ❯

Methods Mentioned

BETA
xenografts
Fluorescence
flow cytometry
protein array
co-immunoprecipitation
confocal microscopy
ELISA
ubiquitination
K689
nuclear magnetic resonance

Software Mentioned

Graphpad Prism
kmplot
Extreme Limiting Dilution Analysis ( ELDA )
IVIS Spectrum
ARRIVE
GSEA
TASSER

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.