Upregulated GPRC5A disrupting the Hippo pathway promotes the proliferation and migration of pancreatic cancer cells via the cAMP-CREB axis.
Upregulated GPRC5A disrupting the Hippo pathway promotes the proliferation and migration of pancreatic cancer cells via the cAMP-CREB axis.
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上调的GPRC 5A破坏Hippo通路通过cAMP-CREB轴促进胰腺癌细胞的增殖和迁移。
DOI：
10.1007/s12672-023-00626-1
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发表时间：
2023-02-03
影响因子：
2.2
通讯作者：
Ma, Mei
中科院分区：
文献类型：
--
作者：
Fang, Weidan;Yu, Xin;Deng, Jun;Yu, Bin;Xiong, Jianping;Ma, Mei
胰腺癌在全球范围内具有很高的死亡率，预计在不久的将来将成为第三大死亡原因。然而，抑制胰腺癌进展的调节机制仍然难以捉摸。目前，探索GPCR（G蛋白偶联受体）的功能和机制是发现有希望的癌症治疗靶点的重要途径。使用实时定量 PCR、免疫组织化学和蛋白质印迹测定来测量 GPRC5A 表达。使用 CCK-8、克隆形成、伤口愈合和 Transwell 测定来评估细胞增殖和迁移。使用胞质/核分布实验来检测蛋白质位置转移。建立胰腺癌异种移植模型以探讨 GPRC5A 在体内的作用。胰腺癌中 GPRC5A 表达增加，破坏 GPRC5A 表达可抑制体内肿瘤生长。从机制上讲，GPRC5A 通过 cAMP-CREB 信号传导正向调节 YAP1 的转录。此外，我们表明，通过抑制 YAP1 表达可以挽救 GPRC5A 在胰腺癌中诱导的增殖和迁移。 GPRC5A与Hippo通路相互作用促进胰腺癌的进展。这些发现揭示了一个重要的串扰模型，并为胰腺癌治疗提供了潜在的靶点。在线版本包含可在 10.1007/s12672-023-00626-1 获取的补充材料。
Pancreatic cancer has a high mortality rate worldwide, and is predicted to be third leading cause of death in the near future. However, the regulatory mechanisms that inhibit the progression of pancreatic cancer remain elusive. Currently, exploring the function and mechanisms of GPCRs (G-protein coupled receptors) is an important way to discover promising therapeutic targets for cancer. GPRC5A expression was measured using real-time quantitative PCR, immunohistochemistry and western blot assays. Cell proliferation and migration were assessed using CCK-8, clone formation, wound-healing and transwell assays. A cytosolic/nuclear distribution experiment was used to detect the protein location transfer. A xenograft model of pancreatic cancer was established to explore the role of GPRC5A in vivo. GPRC5A expression was increased in pancreatic cancer, and disruption of GPRC5A expression inhibited tumor growth in vivo. Mechanistically, GPRC5A positively regulated the transcription of YAP1 through cAMP-CREB signaling. Moreover, we show that the proliferation and migration induced by GPRC5A in pancreatic cancer could be rescued by inhibiting YAP1 expression. GPRC5A interacts with the Hippo pathway to promote the progression of pancreatic cancer. These findings reveal an important crosstalk model and provide potential targets for pancreatic cancer therapy. The online version contains supplementary material available at 10.1007/s12672-023-00626-1.
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影响因子：
10.5
作者：
Meng Z;Moroishi T;Guan KL
通讯作者：
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