Role of MEK-ERK Signaling Mediated Adhesion of Glioma Cells to Extra-cellular Matrix: Possible Implication on Migration and Proliferation

Overview

Journal Ann Neurosci

Publisher Sage Publications

Specialty Neurology

Date 2020 Jan 25

PMID 31975773

Citations 9

Authors

Palaniswamy Ramaswamy

Nandakumar Dalavaikodihalli Nanjaiah

Monjuri Borkotokey

Affiliations

Soon will be listed here.

Abstract

Background: Glioblastoma represents the most common primary brain tumor with a worst prognosis despite developments in neurosurgery and chemoradiotherapy. Detachment of the cells from the primary tumor tissue is a prerequisite for their dispersion and spreading. Initial and incessant dispersal of tumor cells from the primary tumor tissue renders GBM refractory to comprehensive surgical removal and increases the chance of recurrence and poorer prognosis.

Purposes: The current study was designed to investigate the effect of inhibition of MEK-ERK1/2 signaling by PD98059 and U0126 on the growth and migration of glioma cells as well as their adhesion to extracellular matrix.

Methods: MEK-ERK1/2 signaling in U87-MG cells was inhibited by PD98059 and U0126. Migration, proliferation and adhesion were analyzed by scratch-wound assay, MTT assay, cell adhesion assay respectively.

Results: PD98059 and U0126 significantly not only reduced the proliferation of glioma cells and attenuated their migration but also increased their adhesion to gelatin of extracellular matrix.

Conclusion: This study provides the evidence that inhibition of MEK-ERK1/2 signaling enhances the adhesion of glioma cells to gelatin/collagen component of ECM, and decreases the proliferation and migration of the glioma cells. We propose the possible rationale of association between ERK signaling and cell-cell adhesion molecules in glioma microenvironment which regulates the glioma initiation, growth and progression.

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References

Mitra S, Hanson D, Schlaepfer D . Focal adhesion kinase: in command and control of cell motility. Nat Rev Mol Cell Biol. 2005; 6(1):56-68. DOI: 10.1038/nrm1549. View

Kobayashi H, Boelte K, Lin P . Endothelial cell adhesion molecules and cancer progression. Curr Med Chem. 2007; 14(4):377-86. DOI: 10.2174/092986707779941032. View

Shannon S, Jia D, Entersz I, Beelen P, Yu M, Carcione C . Inhibition of glioblastoma dispersal by the MEK inhibitor PD0325901. BMC Cancer. 2017; 17(1):121. PMC: 5303286. DOI: 10.1186/s12885-017-3107-x. View

Cappellari A, Vasques G, Bavaresco L, Braganhol E, Battastini A . Involvement of ecto-5'-nucleotidase/CD73 in U138MG glioma cell adhesion. Mol Cell Biochem. 2011; 359(1-2):315-22. DOI: 10.1007/s11010-011-1025-9. View

Hurmath F, Mittal M, Ramaswamy P, Rao G, Dalavaikodihalli Nanjaiah N . Sevoflurane and thiopental preconditioning attenuates the migration and activity of MMP-2 in U87MG glioma cells. Neurochem Int. 2016; 94:32-8. DOI: 10.1016/j.neuint.2016.02.003. View

Jaiswal J, Shastry A, Ramesh A, Chickabasaviah Y, Arimappamagan A, Santosh V . Spectrum of primary intracranial tumors at a tertiary care neurological institute: A hospital-based brain tumor registry. Neurol India. 2016; 64(3):494-501. DOI: 10.4103/0028-3886.181535. View

Shingu T, Holmes L, Henry V, Wang Q, Latha K, Gururaj A . Suppression of RAF/MEK or PI3K synergizes cytotoxicity of receptor tyrosine kinase inhibitors in glioma tumor-initiating cells. J Transl Med. 2016; 14:46. PMC: 4746796. DOI: 10.1186/s12967-016-0803-2. View

Li C, Zhou Y, Peng X, Du L, Tian H, Yang G . Sulforaphane inhibits invasion via activating ERK1/2 signaling in human glioblastoma U87MG and U373MG cells. PLoS One. 2014; 9(2):e90520. PMC: 3938755. DOI: 10.1371/journal.pone.0090520. View

Zhang X, Zhang W, Cao W, Cheng G, Zhang Y . Glioblastoma multiforme: Molecular characterization and current treatment strategy (Review). Exp Ther Med. 2012; 3(1):9-14. PMC: 3438851. DOI: 10.3892/etm.2011.367. View

10.

Ramaswamy P, Aditi Devi N, Hurmath Fathima K, Dalavaikodihalli Nanjaiah N . Activation of NMDA receptor of glutamate influences MMP-2 activity and proliferation of glioma cells. Neurol Sci. 2013; 35(6):823-9. DOI: 10.1007/s10072-013-1604-5. View

11.

Kim J, Kim Y, Lee S, Park J . The critical role of ERK in death resistance and invasiveness of hypoxia-selected glioblastoma cells. BMC Cancer. 2009; 9:27. PMC: 2645423. DOI: 10.1186/1471-2407-9-27. View

12.

Kohsaka S, Hinohara K, Wang L, Nishimura T, Urushido M, Yachi K . Epiregulin enhances tumorigenicity by activating the ERK/MAPK pathway in glioblastoma. Neuro Oncol. 2014; 16(7):960-70. PMC: 4057138. DOI: 10.1093/neuonc/not315. View

13.

Gao Y, Zhu T, Chen J, Liu L, Ouyang R . Knockdown of collagen α-1(III) inhibits glioma cell proliferation and migration and is regulated by miR128-3p. Oncol Lett. 2018; 16(2):1917-1923. PMC: 6036335. DOI: 10.3892/ol.2018.8830. View

14.

Kumawat R, Gowda S, Debnath E, Rashid S, Niwas R, Gupta Y . Association of Single Nucleotide Polymorphisms (SNPs) in Genes Encoding for Folate Metabolising Enzymes with Glioma and Meningioma in Indian Population. Asian Pac J Cancer Prev. 2018; 19(12):3415-3425. PMC: 6428555. DOI: 10.31557/APJCP.2018.19.12.3415. View

15.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

16.

Maestro R, Shivers R, McDonald W, Maestro A . Dynamics of C6 astrocytoma invasion into three-dimensional collagen gels. J Neurooncol. 2001; 53(2):87-98. DOI: 10.1023/a:1012236830230. View

17.

Shimizu T, Kurozumi K, Ishida J, Ichikawa T, Date I . Adhesion molecules and the extracellular matrix as drug targets for glioma. Brain Tumor Pathol. 2016; 33(2):97-106. DOI: 10.1007/s10014-016-0261-9. View

18.

Liu P, Cai J, Dong D, Chen Y, Liu X, Wang Y . Effects of SOX2 on Proliferation, Migration and Adhesion of Human Dental Pulp Stem Cells. PLoS One. 2015; 10(10):e0141346. PMC: 4619695. DOI: 10.1371/journal.pone.0141346. View

19.

Redman E, Brookes P, Karcz M . Role of p90(RSK) in regulating the Crabtree effect: implications for cancer. Biochem Soc Trans. 2013; 41(1):124-6. PMC: 4030437. DOI: 10.1042/BST20120277. View

20.

Sanclemente M, Francoz S, Esteban-Burgos L, Bousquet-Mur E, Djurec M, Lopez-Casas P . c-RAF Ablation Induces Regression of Advanced Kras/Trp53 Mutant Lung Adenocarcinomas by a Mechanism Independent of MAPK Signaling. Cancer Cell. 2018; 33(2):217-228.e4. DOI: 10.1016/j.ccell.2017.12.014. View