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Article

Drug Resistance in Glioma Cells Induced by a Mesenchymal–Amoeboid Migratory Switch

1
Light Laboratories, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK
2
Leeds Institute of Medical Research at St. James’s, University of Leeds, Leeds LS9 7TF, UK
3
Brown University Cancer Center, Pathology & Laboratory Medicine, Brown University, Providence, RI 02903, USA
4
Harvey Cushing Neuro-Oncology Research Laboratories, Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
5
School of Applied Sciences, University of Huddersfield, Huddersfield HD1 3DH, UK
*
Author to whom correspondence should be addressed.
Current address: Department of Biological and Geographical Sciences, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK.
Academic Editor: Simon J Allison
Biomedicines 2022, 10(1), 9; https://doi.org/10.3390/biomedicines10010009
Received: 17 September 2021 / Revised: 17 December 2021 / Accepted: 19 December 2021 / Published: 22 December 2021
Cancer cell invasion is a precondition for tumour metastasis and represents one of the most devastating characteristics of cancer. The development of drugs targeting cell migration, known as migrastatics, may improve the treatment of highly invasive tumours such as glioblastoma (GBM). In this study, investigations into the role of the cell adhesion protein Cellular communication network factor 1 (CCN1, also known as CYR61) in GBM cell migration uncovered a drug resistance mechanism adopted by cells when treated with the small molecule inhibitor CCG-1423. This inhibitor binds to importin α/β inhibiting the nuclear translocation of the transcriptional co-activator MKL1, thus preventing downstream effects including migration. Despite this reported role as an inhibitor of cell migration, we found that CCG-1423 treatment did not inhibit GBM cell migration. However, we could observe cells now migrating by mesenchymal–amoeboid transition (MAT). Furthermore, we present evidence that CCN1 plays a critical role in the progression of GBM with increased expression in higher-grade tumours and matched blood samples. These findings support a potential role for CCN1 as a biomarker for the monitoring and potentially early prediction of GBM recurrence, therefore as such could help to improve treatment of and increase survival rates of this devastating disease. View Full-Text
Keywords: migration; invasion; glioblastoma; CCN1; mesenchymal–amoeboid transition; biomarker migration; invasion; glioblastoma; CCN1; mesenchymal–amoeboid transition; biomarker
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MDPI and ACS Style

Ketchen, S.E.; Gamboa-Esteves, F.O.; Lawler, S.E.; Nowicki, M.O.; Rohwedder, A.; Knipp, S.; Prior, S.; Short, S.C.; Ladbury, J.E.; Brüning-Richardson, A. Drug Resistance in Glioma Cells Induced by a Mesenchymal–Amoeboid Migratory Switch. Biomedicines 2022, 10, 9. https://doi.org/10.3390/biomedicines10010009

AMA Style

Ketchen SE, Gamboa-Esteves FO, Lawler SE, Nowicki MO, Rohwedder A, Knipp S, Prior S, Short SC, Ladbury JE, Brüning-Richardson A. Drug Resistance in Glioma Cells Induced by a Mesenchymal–Amoeboid Migratory Switch. Biomedicines. 2022; 10(1):9. https://doi.org/10.3390/biomedicines10010009

Chicago/Turabian Style

Ketchen, Sophie E., Filomena O. Gamboa-Esteves, Sean E. Lawler, Michal O. Nowicki, Arndt Rohwedder, Sabine Knipp, Sally Prior, Susan C. Short, John E. Ladbury, and Anke Brüning-Richardson. 2022. "Drug Resistance in Glioma Cells Induced by a Mesenchymal–Amoeboid Migratory Switch" Biomedicines 10, no. 1: 9. https://doi.org/10.3390/biomedicines10010009

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