Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Editorial
. 2018 Sep;10(Suppl 26):S3186-S3191.
doi: 10.21037/jtd.2018.08.25.

Sortilin as a new membrane inhibitor of EGFR trafficking for overcoming resistance to EGFR inhibitors in non-small cell lung cancer

Qianping Li  1   2 , Weijie Ma  2 , Tianhong Li  2   3
Affiliations
Editorial

Sortilin as a new membrane inhibitor of EGFR trafficking for overcoming resistance to EGFR inhibitors in non-small cell lung cancer

Qianping Li et al. J Thorac Dis. 2018 Sep.
No abstract available

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
A schema of sortilin regulating EGFR trafficking (18). Sortilin is mainly localized at the plasma membrane and the trans-Golgi network (TGN). (A) Endocytosis: under normal circumstances, sortilin is essential for EGFR sorting in EGFR endocytosis (B) Exocytosis: upon ligand binding, cell surface EGFRs are activated and internalized, and then either sorted at the early endosome (EE) or cycled continually between the surface of plasma membrane and the TGN via endocytosis and exocytosis. (C) EGFR signaling: the most known EGFR ligand is EGF, which activates the phosphorylation of EGFR tyrosine kinases and downstream signaling pathways, including the Ras/Raf/MEK-ERK/MAP kinase, PI3K/AKT/mTOR, and JAK/STAT pathways, for cell growth, survival, migration, anti-apoptosis, and promoting angiogenesis. Loss of sortilin expression results in failure of EGFR receptor internalization which leads to prolonged or continuous activation of EGFR signaling cascade, enhanced cell proliferation and/or survival, invasion, metastasis, and poor clinical outcomes. The fate of EGFR has important consequences for biological cell outputs: the recycling pathway favoring cell proliferation while the degradative pathway controlling normal cellular homeostasis. Several reported key regulators for each process were listed within this figure (18). Additionally, EGFR may translocate to the nucleus and mitochondria although the transport mechanisms remain to be elucidated. EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; ESCRT, endosomal sorting complex required for transport; MVBs, multivesicular bodies; TGN, the trans-Golgi network.
See this image and copyright information in PMC

Comment on

References

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin 2018;68:7-30. 10.3322/caac.21442 - DOI - PubMed
    1. Global Burden of Disease Cancer Collaboration , Fitzmaurice C, Allen C, et al. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol 2017;3:524-48. 10.1001/jamaoncol.2016.5688 - DOI - PMC - PubMed
    1. Cetin K, Ettinger DS, Hei YJ, et al. Survival by histologic subtype in stage IV nonsmall cell lung cancer based on data from the Surveillance, Epidemiology and End Results Program. Clin Epidemiol 2011;3:139-48. 10.2147/CLEP.S17191 - DOI - PMC - PubMed
    1. Li T, Kung HJ, Mack PC, et al. Genotyping and genomic profiling of non-small-cell lung cancer: implications for current and future therapies. J Clin Oncol 2013;31:1039-49. 10.1200/JCO.2012.45.3753 - DOI - PMC - PubMed
    1. Ma W, Gilligan BM, Yuan J, et al. Current status and perspectives in translational biomarker research for PD-1/PD-L1 immune checkpoint blockade therapy. J Hematol Oncol 2016;9:47. 10.1186/s13045-016-0277-y - DOI - PMC - PubMed