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.
Highlights
Liver cancer is the seventh most common cancer and fourth cause of cancer associated mortality world-wide [1]
ROR1 expression has been associated with mesenchymal/metastatic features of several cancers [20,31,32], but it has not been studied in Hepatocellular carcinoma (HCC) before
Analysis of the RNA-seq data from the “EMBL-EBI Expression Atlas” database pointed out the upregulated expression of ROR1 in HCC tumors compared to normal liver tissues (Figure 1a)
Summary
Liver cancer is the seventh most common cancer and fourth cause of cancer associated mortality world-wide [1]. Hepatocellular carcinoma (HCC) is the most common form of liver cancer. The expression and functional contribution of the receptor tyrosine kinase ROR1 have not been investigated in HCC before. We investigated the expression of ROR1 in HCC cells and assessed its involvement in hepatocarcinogenesis. 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. 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 detected endogenous ROR1 protein in human and mouse HCC cell lines. 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
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