NIBP impacts on the expression of E-cadherin, CD44 and vimentin in colon cancer via the NF-κB pathway.
NIBP, a novel nuclear factor-κB (NF-κB)-inducing kinase (NIK) and IκB kinase β (IKKβ) binding protein, directly interacts with NIK and IKKβ, and acts as the 'bridge' of the NF‑κB classical and alternative signaling pathways. However, its influence on epithelial‑mesenchymal transition markers in colon cancer remains to be fully elucidated. The aim of the present study was to investigate the roles of NIBP impacting on the expression of E‑cadherin, CD44 and vimentin. In the present study, the associations between NIBP and E‑cadherin, CD44 and vimentin in clinical samples were analyzed by making pairwise comparisons between normal colon tissue, non‑metastatic colon cancer tissue and metastatic colon cancer tissue. In in vitro experiments, after changing the expression of NIBP in cells, the protein expression levels of CD44, vimentin, E‑cadherin were analyzed by western blot analysis. The results revealed that the protein expression levels of NIBP, CD44 and vimentin were markedly increased, and E‑cadherin was markedly decreased, in metastatic colon cancer tissue compared with normal colon tissue and non‑metastatic colon cancer tissue. Upregulation of NIBP expression decreased the levels of E‑cadherin, whereas the downregulation of NIBP increased E‑cadherin levels, while no significant differences were observed in the levels of CD44 and vimentin. In addition, cells that were treated with the NF‑κB inhibitor, pyrrolidine dithiocarbamate (PDTC), also tended to exhibit increased levels of CD44 and vimentin expression in the NIBP upregulated expression group (29‑NIBP group) compared with the mock group, whereas the expression levels of E‑cadherin, CD44 and vimentin were similar in the NIBP downregulated expression group (116‑NIBPmir group) and the HCT116 blank control group (116‑mock group) on treatment of the cells with tumor necrosis factor‑α. These findings indicated that NIBP, E‑cadherin, CD44 and vimentin are possibly associated with metastasis in colon cancer. When the NF‑κB pathway is not subjected to any interventions, NIBP may predominantly regulate the NF‑κB classical pathway, rather than the alternative pathway. When the classical pathway was completely inhibited, NIBP was able to activate the NF‑κB alternative pathway. NIBP is therefore necessary for the interaction between the NF‑κB classical and alternative pathways. In conclusion, NIBP impacts on the expression levels of E‑cadherin, CD44 and vimentin via the NF‑κB classical and alternative pathways. Therapeutic regimens for patients with colorectal cancer may comprise NIBP inhibitors in the future.
Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Chun-Yan
CY
Xu
Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Meng-Bin
MB
Qin
Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Lin
L
Tan
Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Shi-Quan
SQ
Liu
Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Jie-An
JA
Huang
D015703:Antigens, CD; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis* / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D014746:Vimentin / Q000096:biosynthesis* / Q000235:genetics
D015703:Antigens, CD; C497483:CD44 protein, human; C513384:CDH1 protein, human; D015820:Cadherins; D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D036341:Intercellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; C503887:TRAPPC9 protein, human; D014746:Vimentin