High eEF1A1 Protein Levels Mark Aggressive Prostate Cancers and the In Vitro Targeting of eEF1A1 Reveals the eEF1A1–actin Complex as a New Potential Target for Therapy
Although the eukaryotic elongation factor eEF1A1 plays a role in various tumours, there is little information on its prognosis/therapeutic value in prostate carcinoma. In high-grade and castration-resistant prostate carcinoma (CRPC), the identification of novel therapeutic markers/targets remains a...
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MDPI AG
2022-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/8/4143 |
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| author | Alessandra Bosutti Barbara Dapas Gabriele Grassi Rossana Bussani Fabrizio Zanconati Fabiola Giudici Cristina Bottin Nicola Pavan Carlo Trombetta Bruna Scaggiante |
| author_facet | Alessandra Bosutti Barbara Dapas Gabriele Grassi Rossana Bussani Fabrizio Zanconati Fabiola Giudici Cristina Bottin Nicola Pavan Carlo Trombetta Bruna Scaggiante |
| author_sort | Alessandra Bosutti |
| collection | DOAJ |
| description | Although the eukaryotic elongation factor eEF1A1 plays a role in various tumours, there is little information on its prognosis/therapeutic value in prostate carcinoma. In high-grade and castration-resistant prostate carcinoma (CRPC), the identification of novel therapeutic markers/targets remains a priority. The expression of eEF1A1 protein was determined in formalin-fixed, paraffin-embedded prostate cancer and hyperplasia tissue by IHC. The role of eEF1A1 was investigated in a cellular model using a DNA aptamer (GT75) we previously developed. We used the aggressive CRPC cancer PC-3 and non-tumourigenic PZHPV-7 lines. Cytotoxicity was measured by the MTS assay and eEF1A1 protein levels by in-cell Western assays. The mRNA levels of eEF1A1 were measured by qPCR and ddPCR. Higher expression of eEF1A1 was found in Gleason 7–8 compared with 4–6 tissues (Gleason ≥ 7, 87% versus Gleason ≤ 6, 54%; <i>p</i> = 0.033). Patients with a high expression of eEF1A1 had a worse clinical outcome. In PC-3, but not in PZHPV-7, GT75 decreased cell viability and increased autophagy and cell detachment. In PC-3 cells, but not in PZHPV-7, GT75 mainly co-localised with the fraction of eEF1A1 bound to actin. Overexpression of the eEF1A1 protein can identify aggressive forms of prostate cancer. The targeting of eEF1A1 by GT75 impaired cell viability in PC-3 cancer cells but not in PZHPV-7 non-tumourigenic cells, indicating a specific role for the protein in cancer survival. The eEF1A1–actin complexes appear to be critical for the viability of PC-3 cancer cells, suggesting that eEF1A1 may be an attractive target for therapeutic strategies in advanced forms of prostate cancer. |
| first_indexed | 2024-03-09T10:34:39Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T10:34:39Z |
| publishDate | 2022-04-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f0f503e4c44347a888412905a2928e9c2023-12-01T21:02:22ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01238414310.3390/ijms23084143High eEF1A1 Protein Levels Mark Aggressive Prostate Cancers and the In Vitro Targeting of eEF1A1 Reveals the eEF1A1–actin Complex as a New Potential Target for TherapyAlessandra Bosutti0Barbara Dapas1Gabriele Grassi2Rossana Bussani3Fabrizio Zanconati4Fabiola Giudici5Cristina Bottin6Nicola Pavan7Carlo Trombetta8Bruna Scaggiante9Department of Life Sciences, University of Trieste, Via Valerio 28 and Via Weiss 1, 34127 Trieste, ItalyDepartment of Life Sciences, University of Trieste, Via Valerio 28 and Via Weiss 1, 34127 Trieste, ItalyDepartment of Life Sciences, University of Trieste, Via Valerio 28 and Via Weiss 1, 34127 Trieste, ItalyDepartment of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Hospital, Strada di Fiume, 447, 34149 Trieste, ItalyDepartment of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Hospital, Strada di Fiume, 447, 34149 Trieste, ItalyDepartment of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Hospital, Strada di Fiume, 447, 34149 Trieste, ItalyDepartment of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Hospital, Strada di Fiume, 447, 34149 Trieste, ItalyDepartment of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Hospital, Strada di Fiume, 447, 34149 Trieste, ItalyDepartment of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Hospital, Strada di Fiume, 447, 34149 Trieste, ItalyDepartment of Life Sciences, University of Trieste, Via Valerio 28 and Via Weiss 1, 34127 Trieste, ItalyAlthough the eukaryotic elongation factor eEF1A1 plays a role in various tumours, there is little information on its prognosis/therapeutic value in prostate carcinoma. In high-grade and castration-resistant prostate carcinoma (CRPC), the identification of novel therapeutic markers/targets remains a priority. The expression of eEF1A1 protein was determined in formalin-fixed, paraffin-embedded prostate cancer and hyperplasia tissue by IHC. The role of eEF1A1 was investigated in a cellular model using a DNA aptamer (GT75) we previously developed. We used the aggressive CRPC cancer PC-3 and non-tumourigenic PZHPV-7 lines. Cytotoxicity was measured by the MTS assay and eEF1A1 protein levels by in-cell Western assays. The mRNA levels of eEF1A1 were measured by qPCR and ddPCR. Higher expression of eEF1A1 was found in Gleason 7–8 compared with 4–6 tissues (Gleason ≥ 7, 87% versus Gleason ≤ 6, 54%; <i>p</i> = 0.033). Patients with a high expression of eEF1A1 had a worse clinical outcome. In PC-3, but not in PZHPV-7, GT75 decreased cell viability and increased autophagy and cell detachment. In PC-3 cells, but not in PZHPV-7, GT75 mainly co-localised with the fraction of eEF1A1 bound to actin. Overexpression of the eEF1A1 protein can identify aggressive forms of prostate cancer. The targeting of eEF1A1 by GT75 impaired cell viability in PC-3 cancer cells but not in PZHPV-7 non-tumourigenic cells, indicating a specific role for the protein in cancer survival. The eEF1A1–actin complexes appear to be critical for the viability of PC-3 cancer cells, suggesting that eEF1A1 may be an attractive target for therapeutic strategies in advanced forms of prostate cancer.https://www.mdpi.com/1422-0067/23/8/4143castration-resistant prostate cancercytotoxicityconfocal microscopyeukaryotic elongation factor 1A1GT75 aptamerimmunohistochemistry |
| spellingShingle | Alessandra Bosutti Barbara Dapas Gabriele Grassi Rossana Bussani Fabrizio Zanconati Fabiola Giudici Cristina Bottin Nicola Pavan Carlo Trombetta Bruna Scaggiante High eEF1A1 Protein Levels Mark Aggressive Prostate Cancers and the In Vitro Targeting of eEF1A1 Reveals the eEF1A1–actin Complex as a New Potential Target for Therapy International Journal of Molecular Sciences castration-resistant prostate cancer cytotoxicity confocal microscopy eukaryotic elongation factor 1A1 GT75 aptamer immunohistochemistry |
| title | High eEF1A1 Protein Levels Mark Aggressive Prostate Cancers and the In Vitro Targeting of eEF1A1 Reveals the eEF1A1–actin Complex as a New Potential Target for Therapy |
| title_full | High eEF1A1 Protein Levels Mark Aggressive Prostate Cancers and the In Vitro Targeting of eEF1A1 Reveals the eEF1A1–actin Complex as a New Potential Target for Therapy |
| title_fullStr | High eEF1A1 Protein Levels Mark Aggressive Prostate Cancers and the In Vitro Targeting of eEF1A1 Reveals the eEF1A1–actin Complex as a New Potential Target for Therapy |
| title_full_unstemmed | High eEF1A1 Protein Levels Mark Aggressive Prostate Cancers and the In Vitro Targeting of eEF1A1 Reveals the eEF1A1–actin Complex as a New Potential Target for Therapy |
| title_short | High eEF1A1 Protein Levels Mark Aggressive Prostate Cancers and the In Vitro Targeting of eEF1A1 Reveals the eEF1A1–actin Complex as a New Potential Target for Therapy |
| title_sort | high eef1a1 protein levels mark aggressive prostate cancers and the in vitro targeting of eef1a1 reveals the eef1a1 actin complex as a new potential target for therapy |
| topic | castration-resistant prostate cancer cytotoxicity confocal microscopy eukaryotic elongation factor 1A1 GT75 aptamer immunohistochemistry |
| url | https://www.mdpi.com/1422-0067/23/8/4143 |
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