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
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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