Human pyruvate dehydrogenase phosphatase 1 (PDP1) plays an important physiological role in energy metabolism; however, its expression and function in human pancreatic adenocarcinoma (PDAC) remain unknown. This study aimed to investigate the expression pattern and mechanisms of action of PDP1 in human PDAC. The expression pattern of PDP1 in PDAC was determined, and its correlation with patient survival was analyzed. Ectopic expression or knockdown of PDP1 was performed, and in vitro proliferation and migration, as well as in vivo tumor growth of PDAC, were measured. The mechanism was studied by biochemical approaches. PDP1 was overexpressed in human PDAC samples, and high expression of PDP1 correlated with poor overall and disease-free survival of PDAC patients. PDP1 promoted the proliferation, colony formation, and invasion of PDAC cells in vitro and facilitated orthotopic tumor growth in vivo. PDP1 accelerated intracellular ATP production, leading to sufficient energy to support rapid cancer progression. mTOR activation was responsible for the PDP1-induced tumor cell proliferation and invasion in PDAC. AMPK was downregulated by PDP1 overexpression, resulting in mTOR activation and cancer progression. Our findings suggested that PDP1 could be a promising diagnostic and therapeutic target for anti-PDAC treatment.

中文翻译：

---

丙酮酸脱氢酶磷酸酶 1 的过表达通过调节能量相关的 AMPK/mTOR 信号通路促进胰腺癌的进展。

人丙酮酸脱氢酶磷酸酶1（PDP1）在能量代谢中起着重要的生理作用；然而，它在人胰腺癌（PDAC）中的表达和功能仍然未知。本研究旨在探讨PDP1在人PDAC中的表达模式和作用机制。确定了 PDAC 中 PDP1 的表达模式，并分析了其与患者生存率的相关性。进行了 PDP1 的异位表达或敲低，并测量了 PDAC 的体外增殖和迁移以及体内肿瘤生长。通过生化方法研究了该机制。PDP1 在人类 PDAC 样本中过度表达，并且 PDP1 的高表达与 PDAC 患者较差的总体和无病生存率相关。PDP1 促进增殖、集落形成、和体外 PDAC 细胞的侵袭并促进体内原位肿瘤的生长。PDP1 加速细胞内 ATP 的产生，从而产生足够的能量来支持癌症的快速进展。mTOR 激活是 PDP1 诱导的 PDAC 中肿瘤细胞增殖和侵袭的原因。AMPK 被 PDP1 过表达下调，导致 mTOR 激活和癌症进展。我们的研究结果表明，PDP1 可能是抗 PDAC 治疗的有希望的诊断和治疗靶点。导致 mTOR 激活和癌症进展。我们的研究结果表明，PDP1 可能是抗 PDAC 治疗的有希望的诊断和治疗靶点。导致 mTOR 激活和癌症进展。我们的研究结果表明，PDP1 可能是抗 PDAC 治疗的有希望的诊断和治疗靶点。