National Clinical Research Center for Child Health, The Children's Hospital, Zhejiang University School of Medicine, No. 3333, Binsheng Road, Hangzhou, 310052, People's Republic of China.
Department of Urology, Third Affiliated Hospital of the Second Military Medical University, Shanghai, 201805, People's Republic of China.
Biol Direct. 2024 Jan 2;19(1):3. doi: 10.1186/s13062-023-00449-8.
As the fifth most common cancer in the world, gastric cancer (GC) ranks as the third major cause of cancer-related death globally. Although surgical resection and chemotherapy still remains the mainstay of potentially curative treatment for GC, chemotherapy resistance and adverse side effects limit their clinical applications. Thus, further investigation of the mechanisms of carcinogenesis in GC and discovery of novel biomarkers is of great concern. We herein report that the elevated expression of GPR137 is correlated with GC. Overexpression of GPR137 potentiates human gastric cancer AGS cell malignancy, including proliferation, migration, invasion, colony formation and xenograft growth in nude mice in vivo, whereas knockout of GPR137 by CRISPR/Cas9 gene editing exerts the opposite effects. Mechanistically, GPR137 could bind to MST, the upstream kinases in Hippo pathway, which disrupts the association of MST with LATS, subsequently activating the transcriptional co-activators, YAP and TAZ, and thereby triggering the target transcription and the alterations in GC cell biological actions consequently. Therefore, our findings may provide with the evidence of developing a potentially novel treatment method with specific target for GC.
作为全球第五大常见癌症，胃癌（GC）是全球癌症相关死亡的第三大主要原因。尽管手术切除和化疗仍然是潜在治愈性治疗 GC 的主要方法，但化疗耐药和不良反应限制了它们的临床应用。因此，进一步研究 GC 致癌机制和发现新型生物标志物受到高度关注。本文报道了 GPR137 的高表达与 GC 相关。GPR137 的过表达增强了人胃癌 AGS 细胞的恶性程度，包括体内裸鼠中的增殖、迁移、侵袭、集落形成和异种移植生长，而 CRISPR/Cas9 基因编辑敲除 GPR137 则产生相反的效果。在机制上，GPR137 可以与 Hippo 通路上游激酶 MST 结合，从而破坏 MST 与 LATS 的结合，随后激活转录共激活因子 YAP 和 TAZ，从而触发靶转录和 GC 细胞生物学行为的改变。因此，我们的研究结果可能为开发针对 GC 的潜在新型靶向治疗方法提供依据。
