Abstract
BackgroundRecently accumulated evidence suggests that Raf kinase inhibitor protein (RKIP) participates in regulation of many signaling pathways and plays an important role in tumorigenesis and tumor metastasis. However, studies investigating the role of RKIP in colorectal cancer have not been reported. The aim of this study was to investigate the role of RKIP on colorectal cancer cell differentiation, progression and its correlation with chemosensitivity.ResultsImmunohistochemical analysis revealed that RKIP expression was higher in non-neoplastic colorectal tissue (NCRCT) and colorectal cancer tissue (CRCT) than that in metastatic lymph node tissue (MLNT) (P <0.05). P-ERK protein expression was higher in MLNT and CRCT than that in NCRCT (P = 0.02). Immunocytochemical analysis further revealed that RKIP expression was higher in the well differentiated cell line SW1116 as compared to that in the poorly differentiated cell line LoVo. Matrigel invasive assay demonstrated that the inhibition of RKIP by short hairpin RNA (shRNA) 271 transfection significantly increased the number of migrated cells (90.67 ± 4.04 vs. 37.33 ± 2.51, P <0.05), whereas over-expression of RKIP by PEBP-1 plasmid transfection significantly suppressed the number of migrated cells (79.24 ± 5.18 vs. 154.33 ± 7.25, P <0.05). Meanwhile, down-regulation of RKIP induced an increase in the cell survival rate by inhibiting apoptosis induced by hydroxycamptothecine.ConclusionsRKIP was also found to be associated with cell differentiation, with a higher activity in well differentiated colorectal cancer cells than in poorly differentiated ones. The upregulated expression of RKIP in colorectal cancer cells inhibited cell invasion and metastasis, while downregulation of RKIP reduced chemosensitivity by inhibiting apoptosis induced by HCPT.
Highlights
Accumulated evidence suggests that Raf kinase inhibitor protein (RKIP) participates in regulation of many signaling pathways and plays an important role in tumorigenesis and tumor metastasis
Detection of RKIP and P-extracellular signal-regulated kinase (ERK) expression in colorectal cancer tissue (CRCT), neoplastic colorectal tissue (NCRCT) and metastatic lymph node tissue (MLNT) by immunostaining The expression of RKIP was found throughout in the cytoplasm of NCRCT and CRCT, with no significant difference between the two
The protein expression of P-ERK was positive in CRCT and MLNT, while it was negative in NCRCT
Summary
Accumulated evidence suggests that Raf kinase inhibitor protein (RKIP) participates in regulation of many signaling pathways and plays an important role in tumorigenesis and tumor metastasis. A vast array of studies have been conducted to understand the role of RKIP in various malignancies such as melanoma [1], prostate cancer [2], Recently, RKIP was found to inhibit proliferation of activated hepatic stellate cells by down-regulation of. RKIP does not appear to play exactly the same role in different cancers and non-malignant cells. This may be because of the diverse molecular functioning milieu, different cell proliferation signaling pathways active in different tissues and other mechanisms that are as yet unknown
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