Reptin drives tumour progression and resistance to chemotherapy in nonsmall cell lung cancer

The European Respiratory Journal
Jan-Henrik MikeschMaria-Francisca Arteaga

Abstract

While targeted nonsmall cell lung cancer (NSCLC) therapies have improved the outcome of defined disease subtypes, prognosis for most patients remains poor. We found the AAA+ ATPase Reptin to be highly expressed in the vast majority of 278 NSCLC tumour samples. Thus, the objective of the study was to assess the role of Reptin in NSCLC.Survival analyses of 1145 NSCLC patients revealed that high RNA expression levels of Reptin are associated with adverse outcome. Knockdown of Reptin in human NSCLC cells impaired growth ex vivo and eliminated engraftment in a xenograft model. Reptin directly interacted with histone deacetylase 1 (HDAC1) as the critical mechanism driving NSCLC tumour progression. Pharmacological disruption of the Reptin/HDAC1 complex resulted in a substantial decrease in NSCLC cell proliferation and induced significant sensitisation to cisplatin.Our results identify Reptin as a novel independent prognostic factor and as a key regulator mediating proliferation and clonal growth of human NSCLC cells ex vivo and in vivo We unveil a Reptin/HDAC1 protein complex whose pharmacological disruption sensitises NSCLC cells to cisplatin, suggesting this approach for application in clinical trials.

References

May 20, 1999·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·J M HarveyD C Allred
Jan 8, 2005·Proceedings of the National Academy of Sciences of the United States of America·J S UngerstedtP A Marks
Feb 27, 2007·Trends in Cell Biology·Peter Gallant
May 13, 2009·The Journal of Biological Chemistry·Sajid RashidMarta Miaczynska
Oct 29, 2010·The New England Journal of Medicine·Eunice L KwakA John Iafrate
Apr 7, 2011·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Yoshihiro MinamiyaJunichi Ogawa
Mar 24, 2012·Cancer Cell·Rebecca S Heist, Jeffrey A Engelman
Sep 29, 2012·Genes & Development·Corrie L Gallant-BehmJoaquín M Espinosa
Nov 13, 2012·Molecular Oncology·Maria NewNicholas B La Thangue
Aug 19, 2014·Nature Reviews. Drug Discovery·Katrina J Falkenberg, Ricky W Johnstone
Jul 15, 2015·The Lancet Oncology·Fred R HirschDavid R Gandara
Jul 23, 2015·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Sara PilottoEmiolio Bria
Aug 28, 2015·PloS One·Lars Henning SchmidtWolfgang Hartmann
May 12, 2016·The New England Journal of Medicine·Charles Swanton, Ramaswamy Govindan
Aug 26, 2010·Pharmaceuticals·Srividya SubramanianRichard L Piekarz
Oct 11, 2016·The New England Journal of Medicine·Martin ReckUNKNOWN KEYNOTE-024 Investigators

❮ Previous
Next ❯

Citations

Sep 20, 2019·Journal of Experimental & Clinical Cancer Research : CR·Meng-Xuan ZhuBin-Bin Liu
Jun 9, 2020·British Journal of Haematology·Matthias FloethLinus Angenendt
Jan 12, 2021·Molecular Therapy. Nucleic Acids·Xiaoxue JiangDongdong Lu

❮ Previous
Next ❯

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.

Related Papers

Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
X LiuM Yang
Lung Cancer : Journal of the International Association for the Study of Lung Cancer
Yoshihiro MinamiyaJunichi Ogawa
© 2022 Meta ULC. All rights reserved