Connective tissue growth factor enhances the migration of gastric cancer through downregulation of E‐cadherin via the NF‐κB pathway

Abstract

Local invasion and distant metastasis are difficult problems for surgical intervention and treatment in gastric cancer. Connective tissue growth factor (CTGF/CCN2) was considered to have an important role in this process. In this study, we demonstrated that expression of CTGF was significantly upregulated in clinical tissue samples of gastric carcinoma (GC) samples. Forced expression of CTGF in AGS GC cells promoted their migration in culture and significantly increased tumor metastasis in nude mice, whereas RNA interference-mediated knockdown of CTGF in GC cells significantly inhibited cell migration in vitro. We disclose that CTGF downregulated the expression of E-cadherin through activation of the nuclear factor-jappa B (NF-jB) pathway. The effects of CTGF in GC cells were abolished by dominant negative IjappaB. Collectively, these data reported here demonstrate CTGF could modulate the NF-jappaB pathway and perhaps be a promising therapeutic target for gastric cancer invasion and metastasis. (Cancer Sci 2011; 102: 104-110) G astric cancer (GC) is one of the most common malignancies in the world, ranking as the second most common cause of death worldwide.(1) The only way for cure is surgery combined with chemotherapy. However, approximately 65% of patients with gastric carcinoma have regional or distant metastases at the time of diagnosis, limiting the chance for complete excision of these tumors and thus making treatment extremely difficult. The 5-year survival rate remains poor for this type of cancer, (2,3) especially in patients with metastatic and advanced stages, ranging 5-15%. (4)

Synergistic Effect of Simvastatin Plus Radiation in Gastric Cancer and Colorectal Cancer: Implications of BIRC5 and Connective Tissue Growth Factor

“…CTGF is a cysteine-rich protein that belongs to the CCN family and is reported to interact with several growth factor signaling pathways, including transforming growth factor-b, bone morphogenetic protein, and Wnt (23)(24)(25). Mao et al reported that CTGF can stimulate nuclear factor-kB signaling and thus contribute to the metastasis of GC (26). There is also a report that CTGF is associated with the radiorecovery response of the early growth plate 2 weeks after irradiation (17).…”

New strategy to control cell migration and metastasis regulated by CCN2/CTGF

“…In chondrosarcoma cells, CCN2/CTGF enhances cell migration by matrix metalloproteinase-13 upregulation through integrin α5β3 [55] and in gastric cancer through downregulation of E-cadherin by NF-κB pathway [56]. Curiously, neutralizing anti-CCN2/CTGF antibody attenuated metastasis pancreatic cancer [57]. In cancer and in metastasis, the role of CCN2/CTGF seems to be the same.…”

A synergistic interaction between transcription factors nuclear factor-κB and signal transducers and activators of transcription 3 promotes gastric cancer cell migration and invasion

“…NF-κB activation has been frequently observed in both gastric cancer cells [13-16] and tumor-infiltrating lymphocytes [17]. In addition, down-regulation of NF-κB has been shown to suppress cell migration and invasion in gastric cancer cells in vitro [16,18]. Thus, modulation of the NF-κB pathway might be a promising therapeutic target for gastric cancer metastasis.…”