Biglycan enhances gastric cancer invasion by activating FAK signaling pathway

Abstract

Biglycan (BGN) is an important member of small leucine-rich proteoglycans family, and has been implicated in oncogenesis and development of various human cancer types. Here we report that BGN promotes tumor invasion and metastasis of gastric cancer both in vitro and in vivo. BGN expression is significantly higher in gastric cancer tissues and associated with lymph node metastasis, depth of tumor invasion and TNM stage. BGN enhances gastric cancer cell wound healing, migration and invasion ability as well as the tube formation ability of endothelial cells in vitro. Animal experiments results in vivo are consistent with outcomes in vitro. BGN induces increased phosphorylation of FAK (Tyr576/577, Tyr925 and Tyr397) and Paxillin. These results indicate that BGN is upregulated, and plays an oncogenic role, in gastric cancer metastasis by activating the FAK signaling pathway.

Knockdown of biglycan expression by RNA interference inhibits the proliferation and invasion of, and induces apoptosis in, the HCT116 colon cancer cell line

“…Biglycan is an important component of the extracellular matrix. Mounting evidence supports the hypothesis that biglycan fulfils an oncogenic role in gastric cancer, and gastric cancer cells exhibited increased motility and invasive properties upon biglycan overexpression (17). In the present study, the shRNA-mediated knockdown of biglycan markedly reduced the spontaneous migration distance and the number of invasive colon cancer cells.…”

“…Previous studies demonstrated that biglycan exerts a distinct role in different tumor entities (15)(16)(17). To further investigate the underlying mechanism of biglycan in colon cancer, the effect of biglycan on colon cancer cell migration and invasion was determined.…”

“…Previous studies indicated that a lack of biglycan was associated with reduced bone mass and osteoporosis (6,7). Previous reports also demonstrated that the expression of biglycan was increased in multiple types of tumor tissue, including liver (8), ovarian (9), endometrial (10), pancreatic (11), gastric (12) and colon cancer (13). These findings suggest an important role for biglycan in the development of cancer, however, the underlying mechanism in colon cancer remains to be fully elucidated.…”

Biglycan enhances the ability of migration and invasion in endometrial cancer

“…Our previous study has found that BGN was higher expressed in endometrial cancer cells, and we also know that carcinomatous stroma and the up-regulation of BGN was significantly associated with poor tumor differentiation and advanced stage of the tumor [13]. Growing evidence has demonstrated that BGN gene is overexpressed in various carcinoma tissues such as pancreatic adenocarcinoma [8], colon tumor [9], intrahepatic cholangiocarcinoma [11], gastric cancer [12], esophageal squamous cell carcinoma [14], and melanoma [15], which have something to do with disease progression in some respects. High BGN levels are harmful in tissue and are considered to shortening patients' survival.…”

“…BGN is found to be expressed on the cell surface and in the extracellular matrices of some specialized cell form, and it is distributed widely, basically presents in every organ in human body, although there is uneven within each organ [6,7]. Recently higher expression of BGN has been detected in several tumor tissue compared with the normal tissue such as pancreatic adenocarcinoma [8], colon tumor [9], ovary cancer [10], intrahepatic cholangiocarcinoma [11], and gastric cancer [12]. The overexpression of BGN in tumor tissues suggests a significant role of BGN in cancer metastasis and progression.…”