EPLIN, a prospective oncogenic molecule with contribution to growth, migration and drug resistance in pancreatic cancer
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 b...
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Nature Portfolio
2024-12-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-81485-w |
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| author | Jianyuan Zeng Cai Wang Fiona Ruge Edison Ke Ji Tracey A. Martin Andrew J. Sanders Shuqin Jia Chunyi Hao Wen G. Jiang |
| author_facet | Jianyuan Zeng Cai Wang Fiona Ruge Edison Ke Ji Tracey A. Martin Andrew J. Sanders Shuqin Jia Chunyi Hao Wen G. Jiang |
| author_sort | Jianyuan Zeng |
| collection | DOAJ |
| description | 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). |
| format | Article |
| id | doaj-art-70e8fa2f5ccf48b08bf7b6274ef9615c |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-70e8fa2f5ccf48b08bf7b6274ef9615c2025-08-20T02:39:38ZengNature PortfolioScientific Reports2045-23222024-12-0114112110.1038/s41598-024-81485-wEPLIN, a prospective oncogenic molecule with contribution to growth, migration and drug resistance in pancreatic cancerJianyuan Zeng0Cai Wang1Fiona Ruge2Edison Ke Ji3Tracey A. Martin4Andrew J. Sanders5Shuqin Jia6Chunyi Hao7Wen G. Jiang8School of Medicine, Cardiff UniversitySchool of Medicine, Cardiff UniversitySchool of Medicine, Cardiff UniversityGastrointestinal Cancer Centre, Peking University Cancer Hospital, Peking University, Fucheng Road, Haidian DistrictSchool of Medicine, Cardiff UniversitySchool of Education and Science, University of GloucestershireGastrointestinal Cancer Centre, Peking University Cancer Hospital, Peking University, Fucheng Road, Haidian DistrictGastrointestinal Cancer Centre, Peking University Cancer Hospital, Peking University, Fucheng Road, Haidian DistrictSchool of Medicine, Cardiff UniversityAbstract 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).https://doi.org/10.1038/s41598-024-81485-wEPLINMigrationPancreatic cancerPIK3sMAPKChemotherapeutic resistance |
| spellingShingle | Jianyuan Zeng Cai Wang Fiona Ruge Edison Ke Ji Tracey A. Martin Andrew J. Sanders Shuqin Jia Chunyi Hao Wen G. Jiang EPLIN, a prospective oncogenic molecule with contribution to growth, migration and drug resistance in pancreatic cancer Scientific Reports EPLIN Migration Pancreatic cancer PIK3s MAPK Chemotherapeutic resistance |
| title | EPLIN, a prospective oncogenic molecule with contribution to growth, migration and drug resistance in pancreatic cancer |
| title_full | EPLIN, a prospective oncogenic molecule with contribution to growth, migration and drug resistance in pancreatic cancer |
| title_fullStr | EPLIN, a prospective oncogenic molecule with contribution to growth, migration and drug resistance in pancreatic cancer |
| title_full_unstemmed | EPLIN, a prospective oncogenic molecule with contribution to growth, migration and drug resistance in pancreatic cancer |
| title_short | EPLIN, a prospective oncogenic molecule with contribution to growth, migration and drug resistance in pancreatic cancer |
| title_sort | eplin a prospective oncogenic molecule with contribution to growth migration and drug resistance in pancreatic cancer |
| topic | EPLIN Migration Pancreatic cancer PIK3s MAPK Chemotherapeutic resistance |
| url | https://doi.org/10.1038/s41598-024-81485-w |
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