TCF7L2 promotes anoikis resistance and metastasis of gastric cancer by transcriptionally activating PLAUR.

Abstract

Gastric cancer (GC) is the most common gastrointestinal malignant tumor, and distant metastasis is a critical factor in the prognosis of patients with GC. Understanding the mechanism of GC metastasis will help improve patient prognosis. Studies have confirmed that urokinase-type plasminogen activator receptor (PLAUR) promotes GC metastasis; however, its relationship with anoikis resistance and associated mechanisms remains unclear. In this study, we demonstrated that PLAUR promotes the anoikis resistance and metastasis of GC cells and identified transcription Factor 7 Like 2 (TCF7L2) as an important transcriptional regulator of PLAUR. We also revealed that TCF7L2 is highly expressed in GC and promotes the anoikis resistance and metastasis of GC cells. Moreover, we found that TCF7L2 transcription activates PLAUR. Finally, we confirmed that TCF7L2 is an independent risk factor for poor prognosis of patients with GC. Our results show that TCF7L2 and PLAUR are candidate targets for developing therapeutic strategies for GC metastasis.

• Authors: Tao Zhang, Bofang Wang, Fei Su, Baohong Gu, Lin Xiang, Lei Gao, Peng Zheng, Xue-Mei Li, Hao Chen
• Journal: International journal of biological sciences (Int J Biol Sci) Vol. 18 Issue 11 Pg. 4560-4577 ( 2022) ISSN: 1449-2288 [Electronic] Australia
• PMID: 35864968 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The author(s).

Chemical References

• PLAUR protein, human
• Receptors, Urokinase Plasminogen Activator
• TCF7L2 protein, human
• Transcription Factor 7-Like 2 Protein
• Plasminogen Activators

Topics

• Anoikis
• Cell Line, Tumor
• Gene Expression Regulation, Neoplastic
• Humans
• Neoplasm Metastasis (genetics)
• Plasminogen Activators
• Receptors, Urokinase Plasminogen Activator (genetics)
• Signal Transduction
• Stomach Neoplasms (genetics, pathology)
• Transcription Factor 7-Like 2 Protein (genetics)