The stem cell factor SOX2 regulates the tumorigenic potential in human gastric cancer cells

Abstract

Gastric cancer (GC) is still one of the most common causes of cancer-related death worldwide, which is mainly attributable to late diagnosis and poor treatment options. Infection with Helicobacter pylori, different environmental factors and genetic alterations are known to influence the risk of developing gastric tumors. However, the molecular mechanisms involved in gastric carcinogenesis are still not fully understood, making it difficult to design targeted therapeutic approaches. Aberrant expression of the specific gastric differentiation marker SOX2 has been observed in stomach cancer. However, the role of SOX2 in gastric tumors has not been well established to date. To elucidate the role of SOX2 in gastric tumorigenesis, SOX2 transcriptional activity was blocked in AZ-521 cells. Interestingly, inhibition of SOX2 reduced cell proliferation and migration, increased apoptosis and induced changes in cell cycle. Blocking of SOX2 also reduced the tumorigenic potential of AZ-521 cells in vivo. In addition, correlation of SOX2 expression and proliferation was observed in a subset of human gastric tumors. Finally, target genes of SOX2 were for the first time identified by RNA microarray in GC cells. Taken together, the results presented here indicate that SOX2 controls several aspects related to GC development and progression by regulating the expression of members of important signaling pathways. These findings could provide new therapeutic options for a subset of GCs exhibiting SOX2 deregulation.

miR340 Suppresses the Stem-like Cell Function of Glioma-Initiating Cells by Targeting Tissue Plasminogen Activator

“…Histopathologically, the transplanted hGICs with miR340 overexpression showed apoptosis in the early stage of transplantation, suggesting that antitumorigenic effects of miR340 in GIC might be partly due to tumor cell apoptosis. Recently, the inhibition of Sox2, which is a stem cell marker, was demonstrated to reduce the tumorigenic potential of human gastric cancer cells (25). In the glioma cell lines, the expression levels of Sox2 were initially quite low; therefore, Sox2 function was likely not highly affected by miR340 in these cell lines.…”

Stomach development, stem cells and disease

“…The role of SOX2 is also confusing, in part because its expression is reduced in some gastric cancers and increased in others. Adding to the uncertainty, SOX2 overexpression in some gastric cancer lines arrests cell replication and induces apoptosis (Otsubo et al, 2008) but inhibition of SOX2 has similar effects in the AZ-521 human gastric cancer cell line (Hutz et al, 2014). The significance of many of these associations is unclear, leaving much to learn about the relationship between developmental regulation and adult gastric disorders.…”

Physcion inhibits the metastatic potential of human colorectal cancer SW620 cells in vitro by suppressing the transcription factor SOX2

“…Interestingly, strong SOX2 expression is associated with many types of human solid tumors, including lung cancer, breast cancer, ovarian carcinoma, pancreatic carcinoma and esophageal carcinoma [7] . Furthermore, recent studies have shown that SOX2 is involved in the biological behaviors of a variety of human malignancies, including proliferation [8] , apoptosis [9,10] , and invasion and metastasis [7] . In terms of CRC, the increased expression of SOX2 is associated with distant metastases and lymph-node metastases in rightsided CRC [11] .…”