Department of Gastroenterology, Affiliated the Second Affiliated Hospital of Chongqing Medical University, PR. China.
Department of Medical Examination Center, Affiliated the Second Affiliated Hospital of Chongqing Medical University, PR. China.
Dig Liver Dis. 2024 Jan;56(1):187-197. doi: 10.1016/j.dld.2023.05.014. Epub 2023 May 25.
Ventricular zone-expressed PH domain-containing protein homologue 1 (VEPH1) is a recently discovered intracellular adaptor protein that plays an important role in human development. It has been reported that VEPH1 is closely related to the process of cellular malignancy, but its role in gastric cancer has not been elucidated. This study investigated the expression and function of VEPH1 in human gastric cancer (GC).
We performed qRT‒PCR, Western blotting, and immunostaining assays in GC tissue samples to evaluate VEPH1 expression. Functional experiments were used to measure the malignancy of GC cells. A subcutaneous tumorigenesis model and peritoneal graft tumour model were established in BALB/c mice to determine tumour growth and metastasis in vivo.
VEPH1 expression is decreased in GC and correlates with the overall survival rates of GC patients. VEPH1 inhibits GC cell proliferation, migration, and invasion in vitro and suppresses tumour growth and metastasis in vivo. VEPH1 regulates the function of GC cells by inhibiting the Hippo-YAP signalling pathway, and YAP/TAZ inhibitor-1 treatment reverses the VEPH1 knockdown-mediated increase in the proliferation, migration and invasion of GC cells in vitro. Loss of VEPH1 is associated with increased YAP activity and accelerated epithelial-mesenchymal transition (EMT) in GC.
VEPH1 inhibited GC cell proliferation, migration, and invasion in vitro and in vivo and exerted its antitumour effects by inhibiting the Hippo-YAP signalling pathway and EMT process in GC.
室管膜表达 PH 结构域蛋白同源物 1(VEPH1)是一种新发现的细胞内衔接蛋白,在人类发育过程中发挥着重要作用。据报道,VEPH1 与细胞恶变过程密切相关,但它在胃癌中的作用尚未阐明。本研究探讨了 VEPH1 在人胃癌(GC)中的表达和功能。
我们采用 qRT-PCR、Western blot 和免疫组化检测 GC 组织样本中 VEPH1 的表达。通过功能实验来测量 GC 细胞的恶性程度。在 BALB/c 小鼠中建立皮下肿瘤发生模型和腹膜移植瘤模型,以确定体内肿瘤生长和转移情况。
VEPH1 在 GC 中表达下调,与 GC 患者的总生存率相关。VEPH1 在体外抑制 GC 细胞增殖、迁移和侵袭,并在体内抑制肿瘤生长和转移。VEPH1 通过抑制 Hippo-YAP 信号通路调节 GC 细胞的功能,而 YAP/TAZ 抑制剂-1 处理可逆转 VEPH1 敲低介导的 GC 细胞增殖、迁移和侵袭能力的增强。VEPH1 的缺失与 GC 中 YAP 活性的增加和上皮间质转化(EMT)的加速相关。
VEPH1 在体外和体内抑制 GC 细胞增殖、迁移和侵袭,并通过抑制 Hippo-YAP 信号通路和 EMT 过程发挥其抗肿瘤作用。