Journal article
Mechanistic insights into epithelial-mesenchymal transition mediated cisplatin resistance in ovarian cancer
Scientific reports, v 15(1), 3053
24 Jan 2025
PMID: 39856185
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Epithelial-mesenchymal transition (EMT) is designated as one of the prime causes of chemoresistance in many cancers. In our previous study we established that cisplatin resistance in ovarian cancer (OC) is associated with EMT using sensitive OV90 cells and its resistant counterparts OV90CisR1 and OV90CisR2. In this study, we revealed through RNAseq analysis that ITGA1 can play essential part in EMT mediated cisplatin resistance in OC. We found large number of EMT related terms predominant in the top gene ontologies (GO). We also found Extracellular matrix (ECM) and actin cytoskeleton genes highly altered in the resistant cells. This was further confirmed by the protein-protein interaction (PPI) analysis where we identified that the core ECM components e.g., collagen, fibronectin, metalloproteases and integrins possessed most interactions. The pathway analysis revealed the Wnt signaling as the leading pathway. Since integrins have significant interaction with Wnt signaling, we focused our study on integrins among which, ITGA1, ITGA6, ITGA11 and ITGAV were primarily altered. We validated our results by western blotting and found that ITGA1 was highly expressed in resistant cells. Additionally, the high ABCA5 (efflux transporter) expression in resistant cells also supports the EMT proposition. The western blotting also revealed high beta-catenin expression in resistant cells confirming the high Wnt signaling activity. Further, we induced xenograft tumors in nude mice. The histopathological analysis confirmed the aggressive nature of resistant tumors and showed the presence of necrotic core which could be implicated to EMT. Finally, the immunohistochemical staining confirmed the high protein expression in resistant tumor.
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Details
- Title
- Mechanistic insights into epithelial-mesenchymal transition mediated cisplatin resistance in ovarian cancer
- Creators
- Taha Umair Wani - Gyeongsang National UniversityHyun-Yi Kim - NGeneS Inc, Ansan 15495, Gyeonggi, South KoreaGeum-Hwa Lee - Jeonbuk National University HospitalYoung Je Lim - Jeonbuk National University HospitalHan-Jung Chae - Jeonbuk Natl Univ, Sch Pharm, Jeonju 54896, Jeollabuk, South KoreaJi-Ye Kim - Inje UniversityHyonok Yoon (Corresponding Author) - Gyeongsang National University
- Publication Details
- Scientific reports, v 15(1), 3053
- Publisher
- Nature Publishing
- Number of pages
- 13
- Grant note
- ICT-2022R1A2C1009939; 2022R1C1C1008833 / Gyeongsang National University Fund for Professors on Sabbatical Leave National Research Foundation of Korea National Research Foundation of Korea (NRF) - Korean Government; National Research Foundation of Korea
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:001406746600018
- Scopus ID
- 2-s2.0-85216999371
- Other Identifier
- 991022197315004721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Oncology