Abstract
BackgroundThe role of CTGF varies in different types of cancer. The purpose of this study is to investigate the involvement of CTGF in tumor progression and prognosis of human nasopharyngeal carcinoma (NPC).Experimental designCTGF expression levels were examined in NPC tissues and cells, nasopharynx (NP) tissues, and NP69 cells. The effects and molecular mechanisms of CTGF expression on cell proliferation, migration, invasion, and cell cycle were also explored.ResultsNPC cells exhibited decreased mRNA expression of CTGF compared to immortalized human nasopharyngeal epithelial cell line NP69. Similarly, CTGF was observed to be downregulated in NPC compared to normal tissues at mRNA and protein levels. Furthermore, reduced CTGF was negatively associated with the progression of NPC. Knocking down CTGF expression enhanced the colony formation, cell migration, invasion, and G1/S cell cycle transition. Mechanistic analysis revealed that CTGF suppression activated FAK/PI3K/AKT and its downstream signals regulating the cell cycle, epithelial-mesenchymal transition (EMT) and MMPs. Finally, DNA methylation microarray revealed a lack of hypermethylation at the CTGF promoter, suggesting other mechanisms are associated with suppression of CTGF in NPC.ConclusionOur study demonstrates that reduced expression of CTGF promoted cell proliferation, migration, invasion and cell cycle progression through FAK/PI3K/AKT, EMT and MMP pathways in NPC.
Highlights
connective tissue growth factor (CTGF) is a cysteine-rich, matrix-associated, heparin-binding protein, and is widely expressed in variety human tissues and organs, such as connective tissue, pancreas, placenta, and lung
Mechanistic analysis revealed that CTGF suppression activated FAK/PI3K/AKT and its downstream signals regulating the cell cycle, epithelialmesenchymal transition (EMT) and MMPs
DNA methylation microarray revealed a lack of hypermethylation at the CTGF promoter, suggesting other mechanisms are associated with suppression of CTGF in nasopharyngeal carcinoma (NPC)
Summary
CTGF is a cysteine-rich, matrix-associated, heparin-binding protein, and is widely expressed in variety human tissues and organs, such as connective tissue, pancreas, placenta, and lung. Its expression has been associated with tumor cell proliferation, adhesion, and angiogenesis [1], [2] and serves as a prognostic marker in many types of human cancer [3,4,5]. CTGF plays different roles in different types of cancer. CTGF functions as a tumor suppressor in lung cancer, ovarian cancer, and oral squamous cell cancer [5], [10], [11]. The expression pattern and functional mechanisms of CTGF in NPC have not been established. The role of CTGF varies in different types of cancer. The purpose of this study is to investigate the involvement of CTGF in tumor progression and prognosis of human nasopharyngeal carcinoma (NPC). The effects and molecular mechanisms of CTGF expression on cell proliferation, migration, invasion, and cell cycle were explored
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