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

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^*

^*Corresponding author for this work

Institute of Life Sciences and Healthcare

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Article number	4926
Number of pages	22
Journal	Cancers
Volume	14
Issue number	19
DOIs	https://doi.org/10.3390/cancers14194926
Publication status	Published - 8 Oct 2022

Keywords

cell–cell adhesion
dysplasia
EMT/MET
PRELP
retinoblastoma
UKRI
MRC
MR/K501268/1

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/cancers14194926

PRELP Regulates Cell–Cell Adhesion PDFFinal published version, 4.75 MBLicence: CC BY

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Hopkins, J., Asada, K., Leung, A., Papadaki, V., Davaapil, H., Morrison, M., Orita, T., Sekido, R., Kosuge, H., Reddy, M. A., Kimura, K., Mitani, A., Tsumoto, K., Hamamoto, R., Sagoo, M. S., & Ohnuma, S. I. (2022). PRELP regulates cell–cell adhesion and EMT and inhibits retinoblastoma progression. Cancers, 14(19), Article 4926. https://doi.org/10.3390/cancers14194926

@article{dfb87ecc07254c329030ce70217be281,

title = "PRELP regulates cell–cell adhesion and EMT and inhibits retinoblastoma progression",

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 M{\"u}ller 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 = "cell–cell adhesion, dysplasia, EMT/MET, PRELP, retinoblastoma, UKRI, MRC, MR/K501268/1",

author = "Jack Hopkins and Ken Asada and Alex Leung and Vasiliki Papadaki and Hongorzul Davaapil and Matthew Morrison and Tomoko Orita and Ryohei Sekido and Hirofumi Kosuge and Reddy, {M. Ashwin} and Kazuhiro Kimura and Akihisa Mitani and Kouhei Tsumoto and Ryuji Hamamoto and Sagoo, {Mandeep S.} and Ohnuma, {Shin Ichi}",

note = "Funding Information: This work is supported by Fight for Sight to S.-i.O. (# 5081/5082 and # 1582/1583), J.H (# 5081/5082), and R.S. (#1582/1583), CHECT to S.-i.O. and M.S. (# NA), Santen to S.-i.O. and A.L (# NA), MRC to S.-i.O. and H.D. (# MR/K501268/1), MEC to S.-i.O. and M.S. (# R150036A/GR000113). M.S is funded by Royal Blind and the Royal College of Surgeons of Edinburgh (# NA). Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2022",

month = oct,

day = "8",

doi = "10.3390/cancers14194926",

language = "English",

volume = "14",

journal = "Cancers",

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TY - JOUR

T1 - PRELP regulates cell–cell adhesion and EMT and inhibits retinoblastoma progression

AU - Hopkins, Jack

AU - Asada, Ken

AU - Leung, Alex

AU - Papadaki, Vasiliki

AU - Davaapil, Hongorzul

AU - Morrison, Matthew

AU - Orita, Tomoko

AU - Sekido, Ryohei

AU - Kosuge, Hirofumi

AU - Reddy, M. Ashwin

AU - Kimura, Kazuhiro

AU - Mitani, Akihisa

AU - Tsumoto, Kouhei

AU - Hamamoto, Ryuji

AU - Sagoo, Mandeep S.

AU - Ohnuma, Shin Ichi

N1 - Funding Information: This work is supported by Fight for Sight to S.-i.O. (# 5081/5082 and # 1582/1583), J.H (# 5081/5082), and R.S. (#1582/1583), CHECT to S.-i.O. and M.S. (# NA), Santen to S.-i.O. and A.L (# NA), MRC to S.-i.O. and H.D. (# MR/K501268/1), MEC to S.-i.O. and M.S. (# R150036A/GR000113). M.S is funded by Royal Blind and the Royal College of Surgeons of Edinburgh (# NA). Publisher Copyright: © 2022 by the authors.

PY - 2022/10/8

Y1 - 2022/10/8

N2 - 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.

AB - 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.

KW - cell–cell adhesion

KW - dysplasia

KW - EMT/MET

KW - PRELP

KW - retinoblastoma

KW - UKRI

KW - MRC

KW - MR/K501268/1

UR - http://www.scopus.com/inward/record.url?scp=85139970353&partnerID=8YFLogxK

U2 - 10.3390/cancers14194926

DO - 10.3390/cancers14194926

M3 - Article

AN - SCOPUS:85139970353

SN - 2072-6694

VL - 14

JO - Cancers

JF - Cancers

IS - 19

M1 - 4926

ER -

PRELP regulates cell–cell adhesion and EMT and inhibits retinoblastoma progression

Abstract

Keywords

UN SDGs

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