4.7 Article

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

Journal

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
Volume 18, Issue 11, Pages 4560-4577

Publisher

IVYSPRING INT PUBL
DOI: 10.7150/ijbs.69933

Keywords

Key words; gastric cancer; urokinase-type plasminogen activator receptor; transcription Factor 7 Like 2; transcription; anoikis

Funding

  1. National Natural Science Foundation of China [81670594, 81470791, 81376597, 81802269]
  2. Major Science and Technology Project of Gansu Province [19ZD2WA001]
  3. Natural Science Foundation of Gansu Province [1606 RJIA328, 20JR5RA352, 20JR10RA686, 21JR7RA386]
  4. Gansu Province Higher Education Innovation Ability Improvement Project [2019B-009, 2020B-009]

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This study identifies urokinase-type plasminogen activator receptor (PLAUR) and transcription Factor 7 Like 2 (TCF7L2) as important factors promoting gastric cancer (GC) metastasis. TCF7L2 regulates PLAUR expression and is an independent risk factor for poor prognosis in GC patients. Therefore, TCF7L2 and PLAUR may be potential targets for therapeutic strategies against GC metastasis.
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.

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