Gastric cancer is the fifth most common cancer worldwide with a poor survival rate. Therefore, it is important to identify predictive and prognostic biomarkers of gastric cancer. Laminin subunit beta 1 (LAMB1) is involved in attachment, migration, and organization during development, and its elevated expression has been associated with several cancers. However, the role and mechanism of LAMB1 in gastric cancer remains unknown. Here, we determined that LAMB1 is upregulated in gastric cancer tissues and contributes to cell growth and motility. Using a public database, we showed that LAMB1 expression was significantly upregulated in gastric cancer compared to normal tissues. LAMB1 was also found to be associated with poor prognosis in patients with gastric cancer. Overexpression of LAMB1 elevated cell proliferation, invasion, and migration; however, knockdown of LAMB1 decreased these effects in gastric cancer cells. U0126, an extracellular signal-regulated kinase (ERK) inhibitor, regulated the expression of LAMB1 in gastric cancer cells. Additionally, we showed that c-Jun directly binds to the LAMB1 promoter as a transcription factor and regulates its gene expression via the ERK pathway in gastric cancer cells. Therefore, our study indicates that LAMB1 promotes cell growth and motility via the ERK/c-Jun axis and is a potential biomarker and therapeutic target of gastric cancer.

Spondin-2 (SPON2) is involved in cancer progression and metastasis of many tumors; however, its role and underlying mechanism in gastric cancer are still obscure. In this study, we investigated the role of SPON2 and related signaling pathway in gastric cancer progression and metastasis. SPON2 expression levels were found to be upregulated in gastric cancer cell lines and patient tissues compared to normal gastric epithelial cells and normal controls. Furthermore, SPON2 silencing was observed to decrease cell proliferation and motility and reduce tumor growth in xenograft mice. Conversely, SPON2 overexpression was found to increase cell proliferation and motility. Subsequently, we focused on regulatory mechanism of SPON2 in gastric cancer. cDNA microarray and in vitro study showed that Notch signaling is significantly correlated to SPON2 expression. Therefore, we confirmed how Notch signaling pathway regulate SPON2 expression using Notch signaling-related transcription factor interaction and reporter gene assay. Additionally, activation of Notch signaling was observed to increase cell proliferation, migration, and invasion through SPON2 expression. Our study demonstrated that Notch signaling-mediated SPON2 upregulation is associated with aggressive progression of gastric cancer. In conclusion, we suggest upregulated SPON2 via Notch signaling as a potential target gene to inhibit gastric cancer progression.

Gastric cancer is a malignant tumor with a high incidence and mortality rate worldwide. Nevertheless, anticancer drugs that can be used for gastric cancer treatment are limited. Therefore, it is important to develop targeted anticancer drugs for the treatment of gastric cancer. Dehydroabietic acid (DAA) is a diterpene found in tree pine. Previous studies have demonstrated that DAA inhibits gastric cancer cell proliferation by inducing apoptosis. However, we did not know how DAA inhibits the proliferation of gastric cancer cells through apoptosis. In this study, we attempted to identify the genes that induce cell cycle arrest and cell death, as well as those which are altered by DAA treatment. DAA-regulated genes were screened using RNA-Seq and differentially expressed genes (DEGs) analysis in AGS cells. RNA-Seq analysis revealed that the expression of survivin, an apoptosis inhibitor, was significantly reduced by DAA treatment. We also confirmed that DAA decreased survivin expression by RT-PCR and Western blotting analysis. In addition, the ability of DAA to inhibit survivin was compared to that of YM-155, a known survivin inhibitor. DAA was found to have a stronger inhibitory effect in comparison with YM-155. DAA also caused an increase in cleaved caspase-3, an apoptosis-activating protein. In conclusion, DAA is a potential anticancer agent for gastric cancer that inhibits survivin expression.