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ROR1 Expression and Its Functional Significance in Hepatocellular Carcinoma Cells

1
Department of Molecular Biology and Genetics, Gebze Technical University, Kocaeli 41400, Turkey
2
Protein Core Facility, Cancer Research UK and Experimental Cancer Medicine Centres, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK
3
Cancer Sciences Unit and Cancer Research UK Centre, University of Southampton, Southampton General Hospital, Somers Cancer Research Building, Mailpoint 824, Southampton SO16 6YD, UK
*
Authors to whom correspondence should be addressed.
Cells 2019, 8(3), 210; https://doi.org/10.3390/cells8030210
Received: 22 February 2019 / Accepted: 26 February 2019 / Published: 2 March 2019
(This article belongs to the Special Issue Epithelial–Mesenchymal Transition and Hallmarks of Cancer)
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Abstract

Background: Hepatocellular carcinoma (HCC) is a common and deadly cancer; however, very little improvement has been made towards its diagnosis and prognosis. The expression and functional contribution of the receptor tyrosine kinase ROR1 have not been investigated in HCC before. Hence, we investigated the expression of ROR1 in HCC cells and assessed its involvement in hepatocarcinogenesis. Methods: Recombinant bacterial ROR1 protein was used as an immunogen to generate ROR1 monoclonal antibodies. ROR1 transcript levels were detected by RT-qPCR and the protein expression of ROR1 in HCC was assessed by Western blotting by using homemade anti-ROR1 monoclonal antibodies. Apoptosis, cell cycle, trans-well migration, and drug efflux assays were performed in shRNA-ROR1 HCC cell clones to uncover the functional contribution of ROR1 to hepatocarcinogenesis. Results: New ROR1 antibodies specifically detected endogenous ROR1 protein in human and mouse HCC cell lines. ROR1-knockdown resulted in decreased proliferation and migration but enhanced resistance to apoptosis and anoikis. The observed chemotherapy-resistant phenotype of ROR1-knockdown cells was due to enhanced drug efflux and increased expression of multi-drug resistance genes. Conclusions: ROR1 is expressed in HCC and contributes to disease development by interfering with multiple pathways. Acquired ROR1 expression may have diagnostic and prognostic value in HCC. View Full-Text
Keywords: HCC; EMT; ROR1; monoclonal antibody; hallmarks of cancer; drug resistance; drug efflux HCC; EMT; ROR1; monoclonal antibody; hallmarks of cancer; drug resistance; drug efflux
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Cetin, M.; Odabas, G.; Douglas, L.R.; Duriez, P.J.; Balcik-Ercin, P.; Yalim-Camci, I.; Sayan, A.E.; Yagci, T. ROR1 Expression and Its Functional Significance in Hepatocellular Carcinoma Cells. Cells 2019, 8, 210.

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