Int J Biol Sci 2022; 18(11):4560-4577. doi:10.7150/ijbs.69933 This issue
1. Department of oncology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China.
2. The second clinical medical college of Lanzhou university, Lanzhou , Gansu, China.
3. Key laboratory of digestive system tumors, Lanzhou University Second Hospital, Lanzhou, Gansu, China.
4. Cancer center, Lanzhou University Second Hospital, Lanzhou, Gansu, China.
*These authors contributed equally to this work.
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.
Keywords: gastric cancer, urokinase-type plasminogen activator receptor, transcription Factor 7 Like 2, transcription, anoikis