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ToolsMeshram, Dipak D., Fanutti, Cristina, Pike, Claire V. S. and Coussons, Peter J. (2024) Membrane association of the short transglutaminase type 2 splice variant (TG2-S) modulates cisplatin resistance in a human hepatocellular carcinoma (HepG2) cell line. Current Issues in Molecular Biology, 46 (5). pp. 4251-4270. ISSN 1467-3037
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Abstract
Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with complex carcinogenesis. Although there has been significant progress in the treatment of HCC over the past decades, drug resistance to chemotherapy remains a major obstacle in its successful management. In this study, we were able to reduce chemoresistance in cisplatin-resistant HepG2 cells by either silencing the expression of transglutaminase type 2 (TG2) using siRNA or by the pre-treatment of cells with the TG2 enzyme inhibitor cystamine. Further analysis revealed that, whereas the full-length TG2 isoform (TG2-L) was almost completely cytoplasmic in its distribution, the majority of the short TG2 isoform (TG2-S) was membrane-associated in both parental and chemoresistant HepG2 cells. Following the induction of cisplatin toxicity in non-chemoresistant parental cells, TG2-S, together with cisplatin, quickly relocated to the cytosolic fraction. Conversely, no cytosolic relocalisation of TG2-S or nuclear accumulation cisplatin was observed, following the identical treatment of chemoresistant cells, where TG2-S remained predominantly membrane-associated. This suggests that the deficient subcellular relocalisation of TG2-S from membranous structures into the cytoplasm may limit the apoptic response to cisplatin toxicity in chemoresistant cells.
| Item Type: | Article |
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| Additional Information: | Data Availability Statement: Any supporting data can be made available upon request. |
| Uncontrolled Keywords: | apoptosis,autophagy,chemoresistance,cisplatin,hepatocellular carcinoma (hcc),hepg2,sub-cellular localisation,transglutaminase 2 (tg2),microbiology,molecular biology,microbiology (medical) ,/dk/atira/pure/subjectarea/asjc/2400/2404 |
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| Depositing User: | LivePure Connector |
| Date Deposited: | 03 Oct 2025 12:30 |
| Last Modified: | 11 Oct 2025 15:34 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/100615 |
| DOI: | 10.3390/cimb46050259 |
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