Caveolin‐1 (Cav‐1) is the principal structural component of caveolae, and its dysregulation occurs in cancer. However, the role of Cav‐1 in pancreatic cancer (PDAC) tumorigenesis and metabolism is largely unknown. In this study, we aimed to investigate the effect of pancreatic stellate cell (PSC) Cav‐1 on PDAC metabolism and aggression. We found that Cav‐1 is expressed at low levels in PDAC stroma and that the loss of stromal Cav‐1 is associated with poor survival. In PSCs, knockdown of Cav‐1 promoted the production of reactive oxygen species (ROS), while ROS production further reduced the expression of Cav‐1. Positive feedback occurs in Cav‐1‐ROS signalling in PSCs, which promotes PDAC growth and induces stroma‐tumour metabolic coupling in PDAC. In PSCs, positive feedback in Cav‐1‐ROS signalling induced a shift in energy metabolism to glycolysis, with up‐regulated expression of glycolytic enzymes (hexokinase 2 (HK‐2), 6‐phosphofructokinase (PFKP) and pyruvate kinase isozyme type M2 (PKM2)) and transporter (Glut1) expression and down‐regulated expression of oxidative phosphorylation (OXPHOS) enzymes (translocase of outer mitochondrial membrane 20 (TOMM20) and NAD(P)H dehydrogenase [quinone] 1 (NQO1)). These events resulted in high levels of glycolysis products such as lactate, which was secreted by up‐regulated monocarboxylate transporter 4 (MCT4) in PSCs. Simultaneously, PDAC cells took up these glycolysis products (lactate) through up‐regulated MCT1 to undergo OXPHOS, with down‐regulated expression of glycolytic enzymes (HK‐2, PFKP and PKM2) and up‐regulated expression of OXPHOS enzymes (TOMM20 and NQO1). Interrupting the metabolic coupling between the stroma and tumour cells may be an effective method for tumour therapy.

中文翻译：

---

PSC 中 Cav-1-ROS 信号传导的正反馈介导 PSC 和肿瘤细胞之间的代谢耦合。

Caveolin-1 (Cav-1) 是小窝的主要结构成分，其失调发生在癌症中。然而，Cav-1 在胰腺癌 (PDAC) 肿瘤发生和代谢中的作用在很大程度上是未知的。在本研究中，我们旨在研究胰腺星状细胞 (PSC) Cav-1 对 PDAC 代谢和攻击的影响。我们发现 Cav-1 在 PDAC 基质中的表达水平较低，并且基质 Cav-1 的缺失与较差的存活率相关。在 PSC 中，Cav-1 的敲低促进了活性氧 (ROS) 的产生，而 ROS 的产生进一步降低了 Cav-1 的表达。正反馈发生在 PSC 中的 Cav-1-ROS 信号传导中，它促进 PDAC 生长并诱导 PDAC 中的基质-肿瘤代谢偶联。在 PSC 中，Cav-1-ROS 信号的正反馈诱导能量代谢转变为糖酵解，糖酵解酶（己糖激酶2（HK-2）、6-磷酸果糖激酶（PFKP）和丙酮酸激酶同工酶M2型（PKM2））和转运蛋白（Glut1）表达上调，氧化磷酸化（OXPHOS）表达下调酶（线粒体外膜转位酶 20 (TOMM20) 和 NAD(P)H 脱氢酶 [醌] 1 (NQO1)）。这些事件导致高水平的糖酵解产物，如乳酸，由 PSC 中上调的单羧酸转运蛋白 4（MCT4）分泌。同时，PDAC 细胞通过上调 MCT1 摄取这些糖酵解产物（乳酸）以进行 OXPHOS，糖酵解酶（HK-2、PFKP 和 PKM2）的表达下调，OXPHOS 酶（TOMM20 和 NQO1）的表达上调）。