Department of oncology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China.
The second clinical medical college of Lanzhou university, Lanzhou , Gansu, China.
Int J Biol Sci. 2022 Jul 11;18(11):4560-4577. doi: 10.7150/ijbs.69933. eCollection 2022.
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.
胃癌（GC）是最常见的胃肠道恶性肿瘤，远处转移是影响 GC 患者预后的关键因素。了解 GC 转移的机制将有助于改善患者的预后。研究证实尿激酶型纤溶酶原激活物受体（PLAUR）促进 GC 转移；然而，其与抗失巢凋亡的关系及其相关机制尚不清楚。在本研究中，我们证实 PLAUR 促进 GC 细胞的抗失巢凋亡和转移，并确定转录因子 7 样 2（TCF7L2）是 PLAUR 的重要转录调节因子。我们还发现 TCF7L2 在 GC 中高表达，并促进 GC 细胞的抗失巢凋亡和转移。此外，我们发现 TCF7L2 转录激活 PLAUR。最后，我们证实 TCF7L2 是 GC 患者预后不良的独立危险因素。我们的研究结果表明，TCF7L2 和 PLAUR 是开发 GC 转移治疗策略的候选靶点。
