Role of Glycosylation in Hypoxia-driven Cell Migration and Invasion

Overview

Journal Cell Adh Migr

Specialty Cell Biology

Date 2018 Jul 18

PMID 30015560

Citations 14

Authors

Cecilia Arriagada

Patricio Silva

Vicente A Torres

Affiliations

Soon will be listed here.

Abstract

Hypoxia, a common condition of the tumor microenvironment, induces changes in the proteome of cancer cells, mainly via HIF-1, a transcription factor conformed by a constitutively expressed β-subunit and an oxygen-regulated α-subunit. In hypoxia, HIF-1α stabilizes, forms the heterodimeric complex with HIF-1β, and binds to Hypoxia Response Elements (HRE), activating gene expression to promote metabolic adaptation, cell invasion and metastasis. Furthermore, the focal adhesion kinase, FAK, is activated in hypoxia, promoting cell migration by mechanisms that remain unclear. In this context, integrins, which are glycoproteins required for cell migration, are possibly involved in hypoxia-induced FAK activation. Evidence suggests that cancer cells have an altered glycosylation metabolism, mostly by the expression of glycosyltransferases, however the relevance of glycosylation is poorly explored in the context of hypoxia. Here, we discuss the role of hypoxia in cancer, and its effects on protein glycosylation, with emphasis on integrins and cell migration.

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References

Keely S, Glover L, MacManus C, Campbell E, Scully M, Furuta G . Selective induction of integrin beta1 by hypoxia-inducible factor: implications for wound healing. FASEB J. 2008; 23(5):1338-46. PMC: 2669428. DOI: 10.1096/fj.08-125344. View

Paul N, Jacquemet G, Caswell P . Endocytic Trafficking of Integrins in Cell Migration. Curr Biol. 2015; 25(22):R1092-105. DOI: 10.1016/j.cub.2015.09.049. View

Semel A, Seales E, Singhal A, Eklund E, Colley K, Bellis S . Hyposialylation of integrins stimulates the activity of myeloid fibronectin receptors. J Biol Chem. 2002; 277(36):32830-6. DOI: 10.1074/jbc.M202493200. View

Dozynkiewicz M, Jamieson N, MacPherson I, Grindlay J, van den Berghe P, von Thun A . Rab25 and CLIC3 collaborate to promote integrin recycling from late endosomes/lysosomes and drive cancer progression. Dev Cell. 2011; 22(1):131-45. PMC: 3507630. DOI: 10.1016/j.devcel.2011.11.008. View

Wickstrom S, Alitalo K, Keski-Oja J . Endostatin associates with integrin alpha5beta1 and caveolin-1, and activates Src via a tyrosyl phosphatase-dependent pathway in human endothelial cells. Cancer Res. 2002; 62(19):5580-9. View

Nonaka M, Fukuda M, Gao C, Li Z, Zhang H, Greene M . Determination of carbohydrate structure recognized by prostate-specific F77 monoclonal antibody through expression analysis of glycosyltransferase genes. J Biol Chem. 2014; 289(23):16478-86. PMC: 4047414. DOI: 10.1074/jbc.M114.559047. View

Kolarich D, Jensen P, Altmann F, Packer N . Determination of site-specific glycan heterogeneity on glycoproteins. Nat Protoc. 2012; 7(7):1285-98. DOI: 10.1038/nprot.2012.062. View

Hamidi H, Pietila M, Ivaska J . The complexity of integrins in cancer and new scopes for therapeutic targeting. Br J Cancer. 2016; 115(9):1017-1023. PMC: 5117799. DOI: 10.1038/bjc.2016.312. View

Rockwell S, Dobrucki I, Kim E, Marrison S, Vu V . Hypoxia and radiation therapy: past history, ongoing research, and future promise. Curr Mol Med. 2009; 9(4):442-58. PMC: 2752413. DOI: 10.2174/156652409788167087. View

10.

Bellis S . Variant glycosylation: an underappreciated regulatory mechanism for beta1 integrins. Biochim Biophys Acta. 2004; 1663(1-2):52-60. DOI: 10.1016/j.bbamem.2004.03.012. View

11.

Saller M, Prall W, Docheva D, Schonitzer V, Popov T, Anz D . Increased stemness and migration of human mesenchymal stem cells in hypoxia is associated with altered integrin expression. Biochem Biophys Res Commun. 2012; 423(2):379-85. DOI: 10.1016/j.bbrc.2012.05.134. View

12.

Semenza G . Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 2003; 3(10):721-32. DOI: 10.1038/nrc1187. View

13.

Kong T, Eltzschig H, Karhausen J, Colgan S, Shelley C . Leukocyte adhesion during hypoxia is mediated by HIF-1-dependent induction of beta2 integrin gene expression. Proc Natl Acad Sci U S A. 2004; 101(28):10440-5. PMC: 478589. DOI: 10.1073/pnas.0401339101. View

14.

Dengler V, Galbraith M, Espinosa J . Transcriptional regulation by hypoxia inducible factors. Crit Rev Biochem Mol Biol. 2013; 49(1):1-15. PMC: 4342852. DOI: 10.3109/10409238.2013.838205. View

15.

Madjd Z, Parsons T, Watson N, Spendlove I, Ellis I, Durrant L . High expression of Lewis y/b antigens is associated with decreased survival in lymph node negative breast carcinomas. Breast Cancer Res. 2005; 7(5):R780-7. PMC: 1242157. DOI: 10.1186/bcr1305. View

16.

Leong H, Chambers A . Hypoxia promotes tumor cell motility via RhoA and ROCK1 signaling pathways. Proc Natl Acad Sci U S A. 2014; 111(3):887-8. PMC: 3903196. DOI: 10.1073/pnas.1322484111. View

17.

Zhao Y, Sato Y, Isaji T, Fukuda T, Matsumoto A, Miyoshi E . Branched N-glycans regulate the biological functions of integrins and cadherins. FEBS J. 2008; 275(9):1939-48. DOI: 10.1111/j.1742-4658.2008.06346.x. View

18.

Ren Y, Hao P, Law S, Sze S . Hypoxia-induced changes to integrin α 3 glycosylation facilitate invasion in epidermoid carcinoma cell line A431. Mol Cell Proteomics. 2014; 13(11):3126-37. PMC: 4223496. DOI: 10.1074/mcp.M114.038505. View

19.

Lee S, Lee Y, Han H . Role of hypoxia-induced fibronectin-integrin β1 expression in embryonic stem cell proliferation and migration: Involvement of PI3K/Akt and FAK. J Cell Physiol. 2010; 226(2):484-93. DOI: 10.1002/jcp.22358. View

20.

Hang Q, Isaji T, Hou S, Wang Y, Fukuda T, Gu J . A Key Regulator of Cell Adhesion: Identification and Characterization of Important -Glycosylation Sites on Integrin α5 for Cell Migration. Mol Cell Biol. 2017; 37(9). PMC: 5394273. DOI: 10.1128/MCB.00558-16. View