open access
Biological functions of nuclear-localized insulin receptor (IR) on A549 lung cancer cells


- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
- Department of Respiratory, Hei long Jiang Province Hospital, Harbin, Hei long Jiang, China
- Hei Long Jiang College of Business and Technology, Hei Long Jiang, China
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
open access
Abstract
Introduction: Under normal physiological conditions, insulin exhibits a series of important biological functions and roles. Recent studies have shown that insulin is also closely related to the occurrence and development of lung cancer. However, until now, the cellular properties of insulin/insulin receptor (IR) on lung cancer have not been fully revealed.
Material and methods: Indirect immunofluorescence, western blot, and other techniques have been used to identify the biological activity of insulin on lung cancer cell lines.
Results: The biological activities of insulin are closely related to its cell behaviour. Therefore, we used lung cancer cell lines as a model to explore the cellular behaviour and properties of insulin/IR in the current study, and the results showed that the IR could internalize into lung cancer cells, and it can also transport into the cell nuclei under insulin treatment. Further study showed that nuclear-localized IR could promote the proliferation of lung cancer cells.
Conclusion: Taken together, this study shows that IR’s nuclear localization is closely related to cell proliferation. This work lays the foundation for further research on the relationship between insulin and the occurrence and development of lung cancer.
Abstract
Introduction: Under normal physiological conditions, insulin exhibits a series of important biological functions and roles. Recent studies have shown that insulin is also closely related to the occurrence and development of lung cancer. However, until now, the cellular properties of insulin/insulin receptor (IR) on lung cancer have not been fully revealed.
Material and methods: Indirect immunofluorescence, western blot, and other techniques have been used to identify the biological activity of insulin on lung cancer cell lines.
Results: The biological activities of insulin are closely related to its cell behaviour. Therefore, we used lung cancer cell lines as a model to explore the cellular behaviour and properties of insulin/IR in the current study, and the results showed that the IR could internalize into lung cancer cells, and it can also transport into the cell nuclei under insulin treatment. Further study showed that nuclear-localized IR could promote the proliferation of lung cancer cells.
Conclusion: Taken together, this study shows that IR’s nuclear localization is closely related to cell proliferation. This work lays the foundation for further research on the relationship between insulin and the occurrence and development of lung cancer.
Keywords
insulin; insulin receptor; lung cancer


Title
Biological functions of nuclear-localized insulin receptor (IR) on A549 lung cancer cells
Journal
Issue
Article type
Original paper
Pages
121-130
Published online
2021-11-04
Page views
4168
Article views/downloads
203
DOI
10.5603/EP.a2021.0099
Pubmed
Bibliographic record
Endokrynol Pol 2022;73(1):121-130.
Keywords
insulin
insulin receptor
lung cancer
Authors
Ren Qiu
Tian Miao
Lin Lin
Zhang Wei


- Hosawi SB, Humphries JD, Coward RJ, et al. Global proteomic analysis of insulin receptor interactors in glomerular podocytes. Wellcome Open Res. 2020; 5: 202.
- Lee J, Pilch PF. The insulin receptor: structure, function, and signaling. Am J Physiol. 1994; 266(2 Pt 1): C319–C334.
- Hall C, Yu H, Choi E. Insulin receptor endocytosis in the pathophysiology of insulin resistance. Exp Mol Med. 2020; 52(6): 911–920.
- Hancock ML, Meyer RC, Mistry M, et al. Insulin Receptor Associates with Promoters Genome-wide and Regulates Gene Expression. Cell. 2019; 177(3): 722–736.e22.
- Frisch CM, Zimmermann K, Zilleßen P, et al. Non-small cell lung cancer cell survival crucially depends on functional insulin receptors. Endocr Relat Cancer. 2015; 22(4): 609–621.
- Argirion I, Weinstein SJ, Männistö S, et al. Serum Insulin, Glucose, Indices of Insulin Resistance, and Risk of Lung Cancer. Cancer Epidemiol Biomarkers Prev. 2017; 26(10): 1519–1524.
- Ho GYF, Zheng SL, Cushman M, et al. Associations of Insulin and IGFBP-3 with Lung Cancer Susceptibility in Current Smokers. J Natl Cancer Inst. 2016; 108(7).
- Vigneri R, Goldfine ID, Frittitta L. Insulin, insulin receptors, and cancer. J Endocrinol Invest. 2016; 39(12): 1365–1376.
- Packham S, Warsito D, Lin Y, et al. Nuclear translocation of IGF-1R via p150(Glued) and an importin-β/RanBP2-dependent pathway in cancer cells. Oncogene. 2015; 34(17): 2227–2238.
- Lawrence MC, McKern NM, Ward CW. Insulin receptor structure and its implications for the IGF-1 receptor. Curr Opin Struct Biol. 2007; 17(6): 699–705.
- Buck E, Gokhale PC, Koujak S, et al. Compensatory insulin receptor (IR) activation on inhibition of insulin-like growth factor-1 receptor (IGF-1R): rationale for cotargeting IGF-1R and IR in cancer. Mol Cancer Ther. 2010; 9(10): 2652–2664.
- Ulanet DB, Ludwig DL, Kahn CR, et al. Insulin receptor functionally enhances multistage tumor progression and conveys intrinsic resistance to IGF-1R targeted therapy. Proc Natl Acad Sci U S A. 2010; 107(24): 10791–10798.
- Lawrence MC, McKern NM, Ward CW. Insulin receptor structure and its implications for the IGF-1 receptor. Curr Opin Struct Biol. 2007; 17(6): 699–705.
- Vigneri PG, Tirrò E, Pennisi MS, et al. The Insulin/IGF System in Colorectal Cancer Development and Resistance to Therapy. Front Oncol. 2015; 5: 230.
- Veiga E, Cossart P. The role of clathrin-dependent endocytosis in bacterial internalization. Trends Cell Biol. 2006; 16(10): 499–504.
- Sui ZH, Xu H, Wang H, et al. Intracellular Trafficking Pathways of : From Clathrin- and Caveolin-Mediated Endocytosis to Endosome and Lysosome. Front Cell Infect Microbiol. 2017; 7: 400.
- Vonderheit A, Helenius A. Rab7 associates with early endosomes to mediate sorting and transport of Semliki forest virus to late endosomes. PLoS Biol. 2005; 3(7): e233.
- McCaffrey M, Bielli A, Cantalupo G, et al. Rab4 affects both recycling and degradative endosomal trafficking. FEBS Letters. 2001; 495(1-2): 21–30.