PRELP Regulates Cell-Cell Adhesion and EMT and Inhibits Retinoblastoma Progression

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

doi:10.3390/cancers14194926

PRELP Regulates Cell-Cell Adhesion and EMT and Inhibits Retinoblastoma Progression

Cancers (Basel). 2022 Oct 8;14(19):4926. doi: 10.3390/cancers14194926.

Authors

Jack Hopkins¹, Ken Asada^{2

3}, Alex Leung¹, Vasiliki Papadaki¹, Hongorzul Davaapil¹, Matthew Morrison¹, Tomoko Orita^{1

4}, Ryohei Sekido¹, Hirofumi Kosuge⁵, M Ashwin Reddy^{6

7}, Kazuhiro Kimura⁴, Akihisa Mitani⁸, Kouhei Tsumoto^{5

9}, Ryuji Hamamoto^{2

3}, Mandeep S Sagoo^{1

6

10}, Shin-Ichi Ohnuma¹

Affiliations

¹ UCL Institute of Ophthalmology, University College London, London EC1V 9EL, UK.
² Cancer Translational Research Team, RIKEN Center for Advanced Intelligence Project, Tokyo 103-0027, Japan.
³ Division of Medical AI Research and Development, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
⁴ Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan.
⁵ School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan.
⁶ Retinoblastoma Unit, Barts Health NHS Trust, Royal London Hospital, London E1 1BB, UK.
⁷ Retinoblastoma Service, Barts Health Trust, Royal London Hospital, London E1 1FR, UK.
⁸ Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
⁹ Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
¹⁰ NIHR, Biomedical Research Centre for Ophthalmology Moorfields Eye Hospital, London EC1V 2PD, UK.

Abstract

Retinoblastoma (RB) is the most common intraocular pediatric cancer. Nearly all cases of RB are associated with mutations compromising the function of the RB1 tumor suppressor gene. We previously demonstrated that PRELP is widely downregulated in various cancers and our in vivo and in vitro analysis revealed PRELP as a novel tumor suppressor and regulator of EMT. In addition, PRELP 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 PRELP in RB through in vitro analysis and next-generation sequencing. Immunostaining revealed that PRELP is expressed in Müller glial cells in the retina. mRNA expression profiling of PRELP^-/- mouse retina and PRELP-treated RB cells found that PRELP contributes to RB progression via regulation of the cancer microenvironment, in which loss of PRELP reduces cell-cell adhesion and facilitates EMT. Our observations suggest that PRELP may have potential as a new strategy for RB treatment.

Keywords: EMT/MET; PRELP; cell–cell adhesion; dysplasia; retinoblastoma.

Abstract

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