<i>PRELP</i> Regulates Cell–Cell Adhesion and EMT and Inhibits Retinoblastoma Progression
Retinoblastoma (RB) is the most common intraocular pediatric cancer. Nearly all cases of RB are associated with mutations compromising the function of the <i>RB1</i> tumor suppressor gene. We previously demonstrated that <i>PRELP</i> is widely downregulated in various cancers...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/19/4926 |
| _version_ | 1797480041650585600 |
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| author | Jack Hopkins Ken Asada Alex Leung Vasiliki Papadaki Hongorzul Davaapil Matthew Morrison Tomoko Orita Ryohei Sekido Hirofumi Kosuge M. Ashwin Reddy Kazuhiro Kimura Akihisa Mitani Kouhei Tsumoto Ryuji Hamamoto Mandeep S. Sagoo Shin-ichi Ohnuma |
| author_facet | Jack Hopkins Ken Asada Alex Leung Vasiliki Papadaki Hongorzul Davaapil Matthew Morrison Tomoko Orita Ryohei Sekido Hirofumi Kosuge M. Ashwin Reddy Kazuhiro Kimura Akihisa Mitani Kouhei Tsumoto Ryuji Hamamoto Mandeep S. Sagoo Shin-ichi Ohnuma |
| author_sort | Jack Hopkins |
| collection | DOAJ |
| description | Retinoblastoma (RB) is the most common intraocular pediatric cancer. Nearly all cases of RB are associated with mutations compromising the function of the <i>RB1</i> tumor suppressor gene. We previously demonstrated that <i>PRELP</i> is widely downregulated in various cancers and our in vivo and in vitro analysis revealed <i>PRELP</i> as a novel tumor suppressor and regulator of EMT. In addition, <i>PRELP</i> is located at chromosome 1q31.1, around a region hypothesized to be associated with the initiation of malignancy in RB. Therefore, in this study, we investigated the role of <i>PRELP</i> in RB through in vitro analysis and next-generation sequencing. Immunostaining revealed that <i>PRELP</i> is expressed in Müller glial cells in the retina. mRNA expression profiling of <i>PRELP<sup>−/−</sup></i> mouse retina and <i>PRELP</i>-treated RB cells found that <i>PRELP</i> contributes to RB progression via regulation of the cancer microenvironment, in which loss of <i>PRELP</i> reduces cell–cell adhesion and facilitates EMT. Our observations suggest that <i>PRELP</i> may have potential as a new strategy for RB treatment. |
| first_indexed | 2024-03-09T21:55:24Z |
| format | Article |
| id | doaj.art-14cb1393977440db97494b5004378901 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T21:55:24Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-14cb1393977440db97494b50043789012023-11-23T19:58:59ZengMDPI AGCancers2072-66942022-10-011419492610.3390/cancers14194926<i>PRELP</i> Regulates Cell–Cell Adhesion and EMT and Inhibits Retinoblastoma ProgressionJack Hopkins0Ken Asada1Alex Leung2Vasiliki Papadaki3Hongorzul Davaapil4Matthew Morrison5Tomoko Orita6Ryohei Sekido7Hirofumi Kosuge8M. Ashwin Reddy9Kazuhiro Kimura10Akihisa Mitani11Kouhei Tsumoto12Ryuji Hamamoto13Mandeep S. Sagoo14Shin-ichi Ohnuma15UCL Institute of Ophthalmology, University College London, London EC1V 9EL, UKCancer Translational Research Team, RIKEN Center for Advanced Intelligence Project, Tokyo 103-0027, JapanUCL Institute of Ophthalmology, University College London, London EC1V 9EL, UKUCL Institute of Ophthalmology, University College London, London EC1V 9EL, UKUCL Institute of Ophthalmology, University College London, London EC1V 9EL, UKUCL Institute of Ophthalmology, University College London, London EC1V 9EL, UKUCL Institute of Ophthalmology, University College London, London EC1V 9EL, UKUCL Institute of Ophthalmology, University College London, London EC1V 9EL, UKSchool of Engineering, The University of Tokyo, Tokyo 113-8656, JapanRetinoblastoma Unit, Barts Health NHS Trust, Royal London Hospital, London E1 1BB, UKDepartment of Ophthalmology, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, JapanDepartment of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, JapanSchool of Engineering, The University of Tokyo, Tokyo 113-8656, JapanCancer Translational Research Team, RIKEN Center for Advanced Intelligence Project, Tokyo 103-0027, JapanUCL Institute of Ophthalmology, University College London, London EC1V 9EL, UKUCL Institute of Ophthalmology, University College London, London EC1V 9EL, UKRetinoblastoma (RB) is the most common intraocular pediatric cancer. Nearly all cases of RB are associated with mutations compromising the function of the <i>RB1</i> tumor suppressor gene. We previously demonstrated that <i>PRELP</i> is widely downregulated in various cancers and our in vivo and in vitro analysis revealed <i>PRELP</i> as a novel tumor suppressor and regulator of EMT. In addition, <i>PRELP</i> is located at chromosome 1q31.1, around a region hypothesized to be associated with the initiation of malignancy in RB. Therefore, in this study, we investigated the role of <i>PRELP</i> in RB through in vitro analysis and next-generation sequencing. Immunostaining revealed that <i>PRELP</i> is expressed in Müller glial cells in the retina. mRNA expression profiling of <i>PRELP<sup>−/−</sup></i> mouse retina and <i>PRELP</i>-treated RB cells found that <i>PRELP</i> contributes to RB progression via regulation of the cancer microenvironment, in which loss of <i>PRELP</i> reduces cell–cell adhesion and facilitates EMT. Our observations suggest that <i>PRELP</i> may have potential as a new strategy for RB treatment.https://www.mdpi.com/2072-6694/14/19/4926<i>PRELP</i>retinoblastomacell–cell adhesiondysplasiaEMT/MET |
| spellingShingle | Jack Hopkins Ken Asada Alex Leung Vasiliki Papadaki Hongorzul Davaapil Matthew Morrison Tomoko Orita Ryohei Sekido Hirofumi Kosuge M. Ashwin Reddy Kazuhiro Kimura Akihisa Mitani Kouhei Tsumoto Ryuji Hamamoto Mandeep S. Sagoo Shin-ichi Ohnuma <i>PRELP</i> Regulates Cell–Cell Adhesion and EMT and Inhibits Retinoblastoma Progression Cancers <i>PRELP</i> retinoblastoma cell–cell adhesion dysplasia EMT/MET |
| title | <i>PRELP</i> Regulates Cell–Cell Adhesion and EMT and Inhibits Retinoblastoma Progression |
| title_full | <i>PRELP</i> Regulates Cell–Cell Adhesion and EMT and Inhibits Retinoblastoma Progression |
| title_fullStr | <i>PRELP</i> Regulates Cell–Cell Adhesion and EMT and Inhibits Retinoblastoma Progression |
| title_full_unstemmed | <i>PRELP</i> Regulates Cell–Cell Adhesion and EMT and Inhibits Retinoblastoma Progression |
| title_short | <i>PRELP</i> Regulates Cell–Cell Adhesion and EMT and Inhibits Retinoblastoma Progression |
| title_sort | i prelp i regulates cell cell adhesion and emt and inhibits retinoblastoma progression |
| topic | <i>PRELP</i> retinoblastoma cell–cell adhesion dysplasia EMT/MET |
| url | https://www.mdpi.com/2072-6694/14/19/4926 |
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