NIK- and IKKβ-binding protein promotes colon cancer metastasis by activating the classical NF-κB pathway and MMPs
Autor: | Side Liu, Meng-Bin Qin, Aimin Li, Jie-An Huang, Chun-Yan Xu, Lin Tan, Shi-Quan Liu |
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Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
Male Pathology Colorectal cancer Gene Expression Matrix metalloproteinase medicine.disease_cause Metastasis chemistry.chemical_compound Mice 0302 clinical medicine Carcinoembryonic antigen Cell Movement Medicine Neoplasm Metastasis Aged 80 and over biology NF-kappa B General Medicine Middle Aged Primary tumor Tumor Burden 030220 oncology & carcinogenesis Colonic Neoplasms Immunohistochemistry Heterografts Intercellular Signaling Peptides and Proteins Female Signal Transduction Adult medicine.medical_specialty 03 medical and health sciences Cell Line Tumor Animals Humans Aged Neoplasm Staging business.industry NF-κB medicine.disease Matrix Metalloproteinases Disease Models Animal 030104 developmental biology chemistry biology.protein Cancer research business Carcinogenesis Carrier Proteins Biomarkers |
Zdroj: | Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 37(5) |
ISSN: | 1423-0380 |
Popis: | 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. |
Databáze: | OpenAIRE |
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