Oncotarget

Research Papers:

Endoplasmic reticulum chaperone prolyl 4-hydroxylase, beta polypeptide (P4HB) promotes malignant phenotypes in glioma via MAPK signaling

Stella Sun, Karrie M.Y. Kiang, Amy S.W. Ho, Derek Lee, Ming-Wai Poon, Fei-Fan Xu, Jenny K.S. Pu, Amanda N.C. Kan, Nikki P.Y. Lee, Xiao-Bing Liu, Kwan Man, Philip J.R. Day, Wai-Man Lui, Ching-Fai Fung and Gilberto K.K. Leung _

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Oncotarget. 2017; 8:71911-71923. https://doi.org/10.18632/oncotarget.18026

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Abstract

Stella Sun1, Karrie M.Y. Kiang1, Amy S.W. Ho1, Derek Lee1, Ming-Wai Poon1, Fei-Fan Xu1, Jenny K.S. Pu1, Amanda N.C. Kan2, Nikki P.Y. Lee1, Xiao-Bing Liu1, Kwan Man1, Philip J.R. Day3, Wai-Man Lui1, Ching-Fai Fung1 and Gilberto K.K. Leung1

1Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong

2Department of Pathology and Clinical Biochemistry, Queen Mary Hospital, Pokfulam, Hong Kong

3The Manchester Institute of Biotechnology, Faculty of Biology, Medicine and Health Sciences, University of Manchester, Manchester, United Kingdom

Correspondence to:

Gilberto K.K. Leung, email: [email protected]

Keywords: P4HB, angiogenesis, glioma, invasion, MAPK signaling

Received: April 19, 2017     Accepted: May 08, 2017     Published: May 19, 2017

ABSTRACT

Endoplasmic reticulum (ER) chaperone Prolyl 4-hydroxylase, beta polypeptide (P4HB) has previously been identified as a novel target for chemoresistance in glioblastoma multiforme (GBM). Yet its functional roles in glioma carcinogenesis remain elusive. In clinical analysis using human glioma specimens and Gene Expression Omnibus (GEO) profiles, we found that aberrant expression of P4HB was correlated with high-grade malignancy and an angiogenic phenotype in glioma. Furthermore, P4HB upregulation conferred malignant characteristics including proliferation, invasion, migration and angiogenesis in vitro, and increased tumor growth in vivo via the mitogen-activated protein kinase (MAPK) signaling pathway. Pathway analysis suggested genetic and pharmacologic inhibition of P4HB suppressed MAPK expression and its downstream targets were involved in angiogenesis and invasion. This is the first study that demonstrates the oncogenic roles of P4HB and its underlying mechanism in glioma. Since tumor invasion and Vascularisation are typical hallmarks in malignant glioma, our findings uncover a promising anti-glioma mechanism through P4HB-mediated retardation of MAPK signal transduction.


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