Tenascin-c knockdown suppresses vasculogenic mimicry of gastric cancer by inhibiting ERK- triggered EMT.

Abstract

Gastric cancer is one of the most common malignancies worldwide and vasculogenic mimicry (VM) is considered to be the leading cause for the failure of anti-angiogenesis therapy in advanced gastric cancer patients. In the present study, we investigate the role of tenascin-c (TNC) in the formation of VM in gastric cancer and found that TNC was upregulated in gastric cancer tissue than in the corresponding adjacent tissues and correlated with VM and poor prognosis of gastric cancer. Furthermore, knockdown of TNC significantly inhibited VM formation and proliferation of gastric cancer cells in vitro and in vivo, with a reduction in cell migration and invasion. Mechanistically, TNC knockdown suppressed the phosphorylation of ERK and subsequently inhibited the process of EMT, both of which play an important role in VM formation. Our results indicated that TNC plays an important role in VM formation in gastric cancer. Combining inhibition of TNC and ERK may be a potential therapeutic approach to inhibit gastric cancer growth and metastasis and decrease antiangiogenic therapeutic resistance.

• Authors: Xing Kang, En Xu, Xingzhou Wang, Lulu Qian, Zhi Yang, Heng Yu, Chao Wang, Chuanfu Ren, Yizhou Wang, Xiaofeng Lu, Xuefeng Xia, Wenxian Guan, Tong Qiao
• Journal: Cell death & disease (Cell Death Dis) Vol. 12 Issue 10 Pg. 890 (09 29 2021) ISSN: 2041-4889 [Electronic] England
• PMID: 34588421 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• Tenascin
• Extracellular Signal-Regulated MAP Kinases

Topics

• Animals
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Epithelial-Mesenchymal Transition
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Humans
• Male
• Mice, Inbred BALB C
• Mice, Nude
• Middle Aged
• Neoplasm Invasiveness
• Peritoneum (pathology)
• Phosphorylation
• Prognosis
• Stomach Neoplasms (genetics, pathology)
• Tenascin (genetics, metabolism)
• Up-Regulation (genetics)
• Mice