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ROR1 associates unfavorable prognosis and promotes lymphoma growth in DLBCL by affecting PI3K/Akt/mTOR signaling pathway
Author(s) -
Mao Yuan,
Xu Li,
Wang Jun,
Zhang Louqian,
Hou Nan,
Xu Juqing,
Wang Lin,
Yang Shu,
Chen Yan,
Xiong Lin,
Zhu Jin,
Fan Weifei,
Xu Jiaren
Publication year - 2019
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.1498
Subject(s) - cancer research , pi3k/akt/mtor pathway , ror1 , diffuse large b cell lymphoma , protein kinase b , cell growth , gene knockdown , medicine , receptor tyrosine kinase , cancer , lymphoma , biology , signal transduction , apoptosis , receptor , platelet derived growth factor receptor , microbiology and biotechnology , growth factor , biochemistry , genetics
The receptor‐tyrosine‐kinase (RTK)‐like orphan receptor 1 (ROR1) is a transmembrane glycoprotein regarded as a tumor‐associated antigen. ROR1 plays an important role in cancer development, but the detailed function of ROR1 in diffuse large B‐cell lymphoma (DLBCL) remains unclear. In this study, we first detected ROR1 expression and evaluated the relationship between ROR1 expression and the clinicopathological characteristics of DLBCL patients. Next we employed shRNA‐mediated knockdown of ROR1 in DLBCL cell line to explore the characteristics of ROR1 in DLBCL development both in vitro and in vivo . The results showed a significantly higher level of ROR1 in DLBCL tissues than in lymphatic hyperplasia tissues. High ROR1 expression was correlated with unfavorable prognosis in DLBCL patients. Furthermore, ROR1 knockdown inhibited the growth and induced the apoptosis in DLBCL cells and xenografts. In addition, shROR1 inhibited activation of the PI3K/Akt/mTOR signaling pathway, both in vitro and in vivo . Taken together, our results suggest that ROR1 is a novel prognostic marker for DLBCL survival and ROR1 significantly promotes DLBCL tumorigenesis by regulating the PI3K/Akt/mTOR signaling pathway. Targeting ROR1 may provide a promising strategy for DLBCL treatment. © 2019 BioFactors, 45(3):416–426, 2019