open access

Ahead of print
Original paper
Submitted: 2021-09-01
Accepted: 2021-09-30
Published online: 2021-11-04
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Biological functions of nuclear-localized insulin receptor (IR) on A549 lung cancers cell

Ren Qiu1, Tian Miao1, Lin Lin1, Zhang Wei1
DOI: 10.5603/EP.a2021.0099
Affiliations
  1. Harbin Medical University, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, People’s Republic of China, 150001 Herbin, China

open access

Ahead of print
Original Paper
Submitted: 2021-09-01
Accepted: 2021-09-30
Published online: 2021-11-04

Abstract

Background: Under normal physiological conditions, insulin exhibits a series of important biological functions and roles. However, 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. 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 behavior. Therefore, we used lung cancer cell lines as a model to explore the cellular behavior 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 relationship between insulin and the occurrence and development of lung cancer.

Abstract

Background: Under normal physiological conditions, insulin exhibits a series of important biological functions and roles. However, 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. 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 behavior. Therefore, we used lung cancer cell lines as a model to explore the cellular behavior 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 relationship between insulin and the occurrence and development of lung cancer.

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Keywords

Insulin; insulin receptor; Lung cancer

About this article
Title

Biological functions of nuclear-localized insulin receptor (IR) on A549 lung cancers cell

Journal

Endokrynologia Polska

Issue

Ahead of print

Article type

Original paper

Published online

2021-11-04

DOI

10.5603/EP.a2021.0099

Keywords

Insulin
insulin receptor
Lung cancer

Authors

Ren Qiu
Tian Miao
Lin Lin
Zhang Wei

References (18)
  1. Hosawi SB, Humphries JD, Coward RJ, et al. Global proteomic analysis of insulin receptor interactors in glomerular podocytes. Wellcome Open Res. 2020; 5: 202.
  2. Lee J, Pilch PF. The insulin receptor: structure, function, and signaling. Am J Physiol. 1994; 266(2 Pt 1): C319–C334.
  3. Hall C, Yu H, Choi E. Insulin receptor endocytosis in the pathophysiology of insulin resistance. Exp Mol Med. 2020; 52(6): 911–920.
  4. 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.
  5. 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.
  6. 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.
  7. 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).
  8. Vigneri R, Goldfine ID, Frittitta L. Insulin, insulin receptors, and cancer. J Endocrinol Invest. 2016; 39(12): 1365–1376.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. Veiga E, Cossart P. The role of clathrin-dependent endocytosis in bacterial internalization. Trends Cell Biol. 2006; 16(10): 499–504.
  16. 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.
  17. 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.
  18. McCaffrey M, Bielli A, Cantalupo G, et al. Rab4 affects both recycling and degradative endosomal trafficking. FEBS Letters. 2001; 495(1-2): 21–30.

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