EPLIN, a Putative Tumour Suppressor in Colorectal Cancer, Implications in Drug Resistance
Colorectal cancer is a serious threat to human health. Poor prognosis and frequently reported drug resistance urges research into novel biomarkers and mechanisms to aid in the understanding of the development and progression of colorectal cancer and to optimise therapeutic strategies. In the current...
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/23/15232 |
| _version_ | 1797463020685754368 |
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| author | Jianyuan Zeng Andrew J. Sanders Lin Ye Rachel Hargest Fiona Ruge Wen G. Jiang |
| author_facet | Jianyuan Zeng Andrew J. Sanders Lin Ye Rachel Hargest Fiona Ruge Wen G. Jiang |
| author_sort | Jianyuan Zeng |
| collection | DOAJ |
| description | Colorectal cancer is a serious threat to human health. Poor prognosis and frequently reported drug resistance urges research into novel biomarkers and mechanisms to aid in the understanding of the development and progression of colorectal cancer and to optimise therapeutic strategies. In the current study, we investigated the roles of a putative tumour suppressor, EPLIN, in colorectal cancer. Our clinical colorectal cancer cohort and online databases revealed a downregulation of EPLIN in colorectal cancer tissues compared with normal tissues. The reduced expression of EPLIN was associated with poor clinical outcomes of patients. In vitro cellular function assays showed that EPLIN elicited an inhibitory effect on cellular growth, adhesion, migration and invasion. Utilising a protein microarray on protein samples from normal and tumour patient tissues suggested HSP60, Her2 and other signalling events were novel potential interacting partners of EPLIN. It was further revealed that EPLIN and HSP60 were negative regulators of Her2 in colorectal cancer cells. The clinical cohort also demonstrated that expression of HSP60 and Her2 affected clinical outcomes, but most interestingly the combination of EPLIN, HSP60 and Her2 was able to identify patients with the most unfavourable clinical outcome by independently predicting patient overall survival and disease free survival. Furthermore, EPLIN and HSP60 exhibited potential to regulate cellular response to chemotherapeutic and EGFR/Her2 targeted therapeutic agents. In conclusion, EPLIN is an important prognostic factor for patients with colon cancer and reduced EPLIN in CRC contributes to aggressive traits of CRC cells and their responses to chemotherapeutic drugs. Collectively, EPLIN is a pivotal factor for the development and progression of colorectal cancer and has important clinical and therapeutic values in this cancer type. |
| first_indexed | 2024-03-09T17:44:45Z |
| format | Article |
| id | doaj.art-a776bbe904bb47a88a414a522e6aaef8 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T17:44:45Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a776bbe904bb47a88a414a522e6aaef82023-11-24T11:15:31ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123231523210.3390/ijms232315232EPLIN, a Putative Tumour Suppressor in Colorectal Cancer, Implications in Drug ResistanceJianyuan Zeng0Andrew J. Sanders1Lin Ye2Rachel Hargest3Fiona Ruge4Wen G. Jiang5School of Medicine, Cardiff University, Henry Wellcome Building, Cardiff CF14 4XN, UKSchool of Medicine, Cardiff University, Henry Wellcome Building, Cardiff CF14 4XN, UKSchool of Medicine, Cardiff University, Henry Wellcome Building, Cardiff CF14 4XN, UKSchool of Medicine, Cardiff University, Henry Wellcome Building, Cardiff CF14 4XN, UKSchool of Medicine, Cardiff University, Henry Wellcome Building, Cardiff CF14 4XN, UKSchool of Medicine, Cardiff University, Henry Wellcome Building, Cardiff CF14 4XN, UKColorectal cancer is a serious threat to human health. Poor prognosis and frequently reported drug resistance urges research into novel biomarkers and mechanisms to aid in the understanding of the development and progression of colorectal cancer and to optimise therapeutic strategies. In the current study, we investigated the roles of a putative tumour suppressor, EPLIN, in colorectal cancer. Our clinical colorectal cancer cohort and online databases revealed a downregulation of EPLIN in colorectal cancer tissues compared with normal tissues. The reduced expression of EPLIN was associated with poor clinical outcomes of patients. In vitro cellular function assays showed that EPLIN elicited an inhibitory effect on cellular growth, adhesion, migration and invasion. Utilising a protein microarray on protein samples from normal and tumour patient tissues suggested HSP60, Her2 and other signalling events were novel potential interacting partners of EPLIN. It was further revealed that EPLIN and HSP60 were negative regulators of Her2 in colorectal cancer cells. The clinical cohort also demonstrated that expression of HSP60 and Her2 affected clinical outcomes, but most interestingly the combination of EPLIN, HSP60 and Her2 was able to identify patients with the most unfavourable clinical outcome by independently predicting patient overall survival and disease free survival. Furthermore, EPLIN and HSP60 exhibited potential to regulate cellular response to chemotherapeutic and EGFR/Her2 targeted therapeutic agents. In conclusion, EPLIN is an important prognostic factor for patients with colon cancer and reduced EPLIN in CRC contributes to aggressive traits of CRC cells and their responses to chemotherapeutic drugs. Collectively, EPLIN is a pivotal factor for the development and progression of colorectal cancer and has important clinical and therapeutic values in this cancer type.https://www.mdpi.com/1422-0067/23/23/15232EPLINcolorectal cancerHSP60Her2drug resistance |
| spellingShingle | Jianyuan Zeng Andrew J. Sanders Lin Ye Rachel Hargest Fiona Ruge Wen G. Jiang EPLIN, a Putative Tumour Suppressor in Colorectal Cancer, Implications in Drug Resistance International Journal of Molecular Sciences EPLIN colorectal cancer HSP60 Her2 drug resistance |
| title | EPLIN, a Putative Tumour Suppressor in Colorectal Cancer, Implications in Drug Resistance |
| title_full | EPLIN, a Putative Tumour Suppressor in Colorectal Cancer, Implications in Drug Resistance |
| title_fullStr | EPLIN, a Putative Tumour Suppressor in Colorectal Cancer, Implications in Drug Resistance |
| title_full_unstemmed | EPLIN, a Putative Tumour Suppressor in Colorectal Cancer, Implications in Drug Resistance |
| title_short | EPLIN, a Putative Tumour Suppressor in Colorectal Cancer, Implications in Drug Resistance |
| title_sort | eplin a putative tumour suppressor in colorectal cancer implications in drug resistance |
| topic | EPLIN colorectal cancer HSP60 Her2 drug resistance |
| url | https://www.mdpi.com/1422-0067/23/23/15232 |
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