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EPLIN, a prospective oncogenic molecule with contribution to growth, migration and drug resistance in pancreatic cancer

Zeng, Jianyuan, Wang, Cai, Ruge, Fiona, Ji, Edison Ke, Martin, Tracey A. ORCID: https://orcid.org/0000-0003-2690-4908, Sanders, Andrew J., Jia, Shuqin, Hao, Chunyi and Jiang, Wen G. ORCID: https://orcid.org/0000-0002-3283-1111 2024. EPLIN, a prospective oncogenic molecule with contribution to growth, migration and drug resistance in pancreatic cancer. Scientific Reports 14 (1) , 30850. 10.1038/s41598-024-81485-w

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Abstract

Most pancreatic cancer patients are diagnosed at advanced stages, with poor survival rates and drug resistance making pancreatic cancer one of the highest causes of cancer death in the UK. Understanding the underlying mechanism behind its carcinogenesis, metastasis and drug resistance has become an essential task for researchers. We have discovered that a well-established tumour suppressor, EPLIN, has an oncogenic rather than suppressive role in pancreatic cancer. Notably, upregulation of EPLIN was observed in pancreatic cancer samples compared to normal samples at RNA and protein levels. Moreover, the presence of EPLIN resulted in poor clinical outcomes in patients. We also report that inhibition of EPLIN led to reduced cellular growth and migration in pancreatic cancer cells. EPLIN regulates expression and phosphorylation levels of several key players in MAPK and PIK3CA-AKT signalling pathways, as well as key contributors of EMT. Furthermore, EPLIN mediates the inhibitory ability PIK3 kinases, MEK and ERK inhibitors have on cell migration. EPLIN was also found to have an impact on pancreatic cancer cells response to chemotherapeutic and EGFR/HER2 targeted therapeutic agents, namely gemcitabine, fluorouracil (5FU) and neratinib (Nerlynx).

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Publisher: Nature Publishing Group
ISSN: 2045-2322
Date of First Compliant Deposit: 6 January 2025
Date of Acceptance: 26 November 2024
Last Modified: 06 Jan 2025 16:22
URI: https://orca.cardiff.ac.uk/id/eprint/175041

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