Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2022

01-12-2022 | Lung Cancer | Research

Downregulation of NEDD4L by EGFR signaling promotes the development of lung adenocarcinoma

Authors: Guoyin Li, Zewen Song, Changjing Wu, XiaoYan Li, Liping Zhao, Binghua Tong, Zhenni Guo, Meiqing Sun, Jin Zhao, Huina Zhang, Lintao Jia, Shengqing Li, Lei Wang

Published in: Journal of Translational Medicine | Issue 1/2022

Login to get access

Abstract

Cumulative evidence indicates that the abnormal regulation of the NEDD4 family of E3-ubiquitin ligases participates in the tumorigenesis and development of cancer. However, their role in lung adenocarcinoma (LUAD) remains unclear. This study comprehensively analyzed the NEDD4 family in LUAD data sets from public databases and found only NEDD4L was associated with the overall survival of LUAD patients. Gene set enrichment analysis (GSEA) indicated that NEDD4L might be involved in the regulation of mTORC1 pathway. Both cytological and clinical assays showed that NEDD4L inhibited the activity of the mTOR signaling pathway. In vivo and in vitro experiments showed that NEDD4L could significantly inhibit the proliferation of LUAD cells. In addition, this study also found that the expression of NEDD4L was regulated by EGFR signaling. These findings firstly revealed that NEDD4L mediates an interplay between EGFR and mTOR pathways in LUAD, and suggest that NEDD4L held great potential as a novel biomarker and therapeutic target for LUAD.
Appendix
Available only for authorised users
Literature
1.
Bray F, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.PubMed
2.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7–34.PubMed
3.
4.
5.
Wang Y, et al. HECT E3 ubiquitin ligases - emerging insights into their biological roles and disease relevance. J Cell Sci. 2020;133:7.
6.
7.
Qu MH, et al. miR-93 promotes TGF-beta-induced epithelial-to-mesenchymal transition through downregulation of NEDD4L in lung cancer cells. Tumour Biol. 2016;37(4):5645–51.CrossRefPubMed
8.
Yang S, et al. Novel genetic variants in KIF16B and NEDD4L in the endosome-related genes are associated with nonsmall cell lung cancer survival. Int J Cancer. 2020;147(2):392–403.CrossRefPubMed
9.
10.
Wang L, et al. ARHGAP24 inhibits cell proliferation and cell cycle progression and induces apoptosis of lung cancer via a STAT6-WWP2-p27 axis. Carcinogenesis. 2020;41(5):711–21.CrossRefPubMed
11.
Li H, et al. Smurf1 regulates lung cancer cell growth and migration through interaction with and ubiquitination of PIPKIgamma. Oncogene. 2017;36(41):5668–80.CrossRefPubMed
12.
Chae DK, et al. MiR-195 and miR-497 suppress tumorigenesis in lung cancer by inhibiting SMURF2-induced TGF-beta receptor I ubiquitination. Mol Oncol. 2019;13(12):2663–78.CrossRefPubMedPubMedCentral
13.
Lu C, et al. E3 ubiquitin ligase HECW1 promotes the metastasis of non-small cell lung cancer cells through mediating the ubiquitination of Smad4. Biochem Cell Biol. 2021;8:1–7.
14.
Li PF, Zhang QG. Inhibition of ITCH suppresses proliferation and induces apoptosis of lung cancer cells. Cell Physiol Biochem. 2018;48(4):1703–9.CrossRefPubMed
15.
Janne PA, Engelman JA, Johnson BE. Epidermal growth factor receptor mutations in non-small-cell lung cancer: implications for treatment and tumor biology. J Clin Oncol. 2005;23(14):3227–34.CrossRefPubMed
16.
Fu H, et al. Aldolase A promotes proliferation and G1/S transition via the EGFR/MAPK pathway in non-small cell lung cancer. Cancer Commun (Lond). 2018;38(1):18.CrossRef
17.
Liu R, et al. Characteristics of TGFBR1-EGFR-CTNNB1-CDH1 signaling Axis in Wnt-regulated invasion and migration in lung cancer. Cell Transplant. 2020;29:963689720969167.PubMed
18.
Shah KN, et al. Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer. Nat Med. 2019;25(1):111–8.CrossRefPubMed
19.
Murugan AK. mTOR: role in cancer, metastasis and drug resistance. Semin Cancer Biol. 2019;59:92–111.CrossRefPubMed
20.
Avruch J, et al. Insulin and amino-acid regulation of mTOR signaling and kinase activity through the Rheb GTPase. Oncogene. 2006;25(48):6361–72.CrossRefPubMed
21.
22.
Deng L, et al. Ubiquitination of Rheb governs growth factor-induced mTORC1 activation. Cell Res. 2019;29(2):136–50.CrossRefPubMed
23.
Hong SY, et al. Upregulation of E3 Ubiquitin Ligase CBLC Enhances EGFR dysregulation and signaling in lung adenocarcinoma. Cancer Res. 2018;78(17):4984–96.CrossRefPubMed
24.
Zhang J, et al. Systematic analysis of the ABC transporter family in hepatocellular carcinoma reveals the importance of ABCB6 in regulating ferroptosis. Life Sci. 2020;257:118131.CrossRefPubMed
25.
Li GY, et al. Long non-coding RNAs AC0269041 and UCA1: a “one-two punch” for TGF-beta-induced SNAI2 activation and epithelial-mesenchymal transition in breast cancer. Theranostics. 2018;8(10):2846–61.CrossRefPubMedPubMedCentral
26.
27.
28.
Li G, et al. Sp1-mediated epigenetic dysregulation dictates HDAC inhibitor susceptibility of HER2-overexpressing breast cancer. Int J Cancer. 2019;145(12):3285–98.CrossRefPubMed
29.
30.
Mari S, et al. Structural and functional framework for the autoinhibition of Nedd4-family ubiquitin ligases. Structure. 2014;22(11):1639–49.CrossRefPubMed
31.
Chen C, Matesic LE. The Nedd4-like family of E3 ubiquitin ligases and cancer. Cancer Metastasis Rev. 2007;26(3–4):587–604.CrossRefPubMed
32.
Nalepa G, Rolfe M, Harper JW. Drug discovery in the ubiquitin-proteasome system. Nat Rev Drug Discov. 2006;5(7):596–613.CrossRefPubMed
33.
Broix L, et al. Mutations in the HECT domain of NEDD4L lead to AKT-mTOR pathway deregulation and cause periventricular nodular heterotopia. Nat Genet. 2016;48(11):1349–58.CrossRefPubMedPubMedCentral
34.
Yu JS, Cui W. Proliferation, survival and metabolism: the role of PI3K/AKT/mTOR signalling in pluripotency and cell fate determination. Development. 2016;143(17):3050–60.CrossRefPubMed
35.
Wang X, et al. Decreased expression of NEDD4L contributes to NSCLC progression and metastasis. Biochem Biophys Res Commun. 2019;513(2):398–404.CrossRefPubMed
36.
Uribe ML, Marrocco I, Yarden Y. EGFR in Cancer: Signaling Mechanisms, Drugs, and Acquired Resistance. Cancers (Basel). 2021;13:11.CrossRef
37.
38.
Arthur-Farraj PJ, et al. Changes in the coding and non-coding transcriptome and DNA methylome that define the Schwann cell repair phenotype after nerve injury. Cell Rep. 2017;20(11):2719–34.CrossRefPubMedPubMedCentral
39.
40.
Ramaiah MJ, Kumar KR. mTOR-Rictor-EGFR axis in oncogenesis and diagnosis of glioblastoma multiforme. Mol Biol Rep. 2021;48(5):4813–35.CrossRefPubMed
41.
Cui J, Shen HM, Lim L. The role of autophagy in liver cancer: crosstalk in signaling pathways and potential therapeutic targets. Pharmaceuticals (Basel). 2020;13:12.CrossRef
Metadata
Title
Downregulation of NEDD4L by EGFR signaling promotes the development of lung adenocarcinoma
Authors
Guoyin Li
Zewen Song
Changjing Wu
XiaoYan Li
Liping Zhao
Binghua Tong
Zhenni Guo
Meiqing Sun
Jin Zhao
Huina Zhang
Lintao Jia
Shengqing Li
Lei Wang
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2022
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-022-03247-4

Other articles of this Issue 1/2022

Journal of Translational Medicine 1/2022 Go to the issue

Research

Enhanced DNA and RNA pathogen detection via metagenomic sequencing in patients with pneumonia

Research

Small and long RNA transcriptome of whole human cerebrospinal fluid and serum as compared to their extracellular vesicle fractions reveal profound differences in expression patterns and impacts on biological processes

Research

Bladder cancer-derived exosomal KRT6B promotes invasion and metastasis by inducing EMT and regulating the immune microenvironment

Research

Evaluation of the effects of meteorological factors on COVID-19 prevalence by the distributed lag nonlinear model

Research

Acidic ascites inhibits ovarian cancer cell proliferation and correlates with the metabolomic, lipidomic and inflammatory phenotype of human patients

Research

Transdermal deferoxamine administration improves excisional wound healing in chronically irradiated murine skin
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits