title: NIK- and IKKβ-binding protein promotes colon cancer metastasis by activating the classical NF-κB pathway and MMPs.
abstract: The nuclear factor (NF)-κB pathway has been implicated in colorectal cancer (CRC) tumorigenesis. Here, we investigated the role of a novel NIK- and IKKβ-binding protein (NIBP) in CRC metastasis through activation of the canonical NF-κB pathway. NIBP, p-p65, and matrix metalloproteases (MMPs) were assessed by immunohistochemistry in 114 CRC tissues, and the time to metastasis was recorded after surgery. Furthermore, the activity of the NF-κB pathway, MMP expression, and the metastatic potential of HT-29 cells overexpressing NIBP after treatment with the NF-κB inhibitor pyrrolidinecarbodithioic acid (PDTC) were examined in vitro and in vivo. NIBP-positive CRC exhibited a higher rate of metastasis, and the time to metastasis of NIBP-positive patients was shorter in the early tumor, lymph node, metastasis (TNM) stages (I and II), while NIBP and p-p65 expression was higher in later TNM stages (III and IV). However, there was no difference in terms of the positive rate of NIBP, p-p65, MMP-2, and serum carcinoembryonic antigen (CEA) level was no difference in the pathological type, gender, tumor location, or size. The NF-κB pathway, MMP-2 and MMP-9 activity, and cell motility and invasion were increased in NIBP-overexpressing cells, even after PDTC treatment. Moreover, these cells exhibited high metastasis in mice, and p-p65, MMP-2, and MMP-9 expression levels were elevated in the primary tumor and liver metastases. In conclusion, NIBP overexpression increases the CRC metastatic potential through activation of the NF-κB pathway and increasing MMP-2 and MMP-9 expression. In addition, NIBP overexpression, at least in part, may reduce inhibition of the canonical NF-κB pathway and MMPs caused by PDTC treatment.
authors.affiliation: Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510000, People's Republic of China.|Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University, Nanning, 530000, People's Republic of China.
authors.forename: Mengbin
authors.initials: M
authors.lastname: Qin
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University, Nanning, 530000, People's Republic of China.
authors.forename: Shiquan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510000, People's Republic of China.
authors.forename: Aimin
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University, Nanning, 530000, People's Republic of China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University, Nanning, 530000, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University, Nanning, 530000, People's Republic of China. hjagxmu@163.com.
authors.forename: Jiean
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510000, People's Republic of China. liuside2011@163.com.
authors.forename: Side
authors.initials: S
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015415:Biomarkers; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D003110:Colonic Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D015398:Signal Transduction; D047368:Tumor Burden
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D016328:NF-kappa B; C503887:TRAPPC9 protein, human; D020782:Matrix Metalloproteinases
keywords: Colorectal cancer; MMP; Metastasis; NF-κB; NIBP