MMP‐11 promotes papillary thyroid cell proliferation and invasion via the NF‐κB pathway

Abstract

Papillary thyroid carcinoma (PTC) is the most common form of thyroid cancer, and its incidence is on the rise. It has been reported that some matrix metalloproteinases (MMPs) are abnormally expressed in PTC and can be used as diagnostic markers. However, few studies have explored the underlying mechanisms by which MMPs promote tumor progression. In this study, we used microarray analysis to compare the variations of gene expression within the PTC cell populations and their adjacent normal tissues and found that MMP-11 was the most differentially expressed MMP. To investigate the role of MMP-11 in the mediation of thyroid cancer cell development, pEnter-MMP-11 plasmid, and MMP-11 small interfering RNA were applied to up- and downregulate MMP-11 expression of in cultured PTC cell lines K1 and BCPAP. The results suggested that the levels of proliferation and migration of cells transfected with MMP-11 siRNA were significantly reduced, while the levels in MMP-11-plasmid-transfected cells were increased. In terms of the mechanism, experimental data showed that the change in cyclin D1 is consistent with MMP-11 expression, which may explain the changes in proliferation. In addition, Western blot assay was conducted to analyze the p65 and activated (phospho-) p65 protein levels concomitant with MMP-11 adjustments. Variations in intracellular MMP-11 significantly altered the amount of phospho-p65 in thyroid cells, while p65 knockdown did not affect MMP-11 expression. These results suggest that MMP-11 is located upstream of p65 and regulates its activity. Interestingly, the data for the Transwell assay suggested that MMP-11 regulatory migration is also associated with the NF-κB p65 signaling pathway. In conclusion, this report describes the important role of MMP-11 in the regulation of thyroid cell proliferation and migration. Mechanistic studies have shown that cyclin D1 and p65 are important mediators in the processes, which provides a new way to study the mechanism of MMPs promoting the progression of thyroid cancer.

Overexpression of B7‑H4 promotes renal cell carcinoma progression by recruiting tumor‑associated neutrophils via upregulation of CXCL8

“…MMPs are a family of enzymes responsible for the degradation of a wide spectrum of extracellular matrix and non-matrix proteins ( 46 ). During carcinogenesis, MMPs can regulate the microenvironment and contribute to several critical steps in cancer development via their involvement in cell proliferation, differentiation, apoptosis, invasion, migration and immune surveillance ( 46 – 48 ). Thus, upregulated MMP7 expression by B7-H4 may serve an important role in tumor progression.…”

NF-κB signaling and crosstalk during carcinogenesis

“…Furthermore, NF-jB has been reported in a number of adenocarcinoma cell lines [53] and NF-jB activity was associated with cancers of the breast [54][55][56][57][58][59][60], ovaries [61,62], endometrium [63], prostate [64][65][66], thyroid [67][68][69][70], pancreas [71][72][73][74], squamous cell carcinoma (SCC) [75,76], esophagus [77][78][79], stomach [80], colorectum [61,[81][82][83], liver [84][85][86], kidneys [87][88][89], bladder [90], lymphoma [91][92][93][94][95], leukemia [96][97][98], multiple myeloma [99][100]…”