Pancreatic cancer stem cells (PCSCs) play a key role in the aggressiveness of pancreatic ductal adenocarcinomas (PDAC); however, little is known about their signaling and metabolic pathways. Here we show that PCSCs have specific and common proteome and lipidome modulations. PCSCs displayed downregulation of lactate dehydrogenase A chain, and upregulation of trifunctional enzyme subunit alpha. The upregulated proteins of PCSCs are mainly involved in fatty acid (FA) elongation and biosynthesis of unsaturated FAs. Accordingly, lipidomics reveals an increase in long and very long-chain unsaturated FAs, which are products of fatty acid elongase-5 predicted as a key gene. Moreover, lipidomics showed the induction in PCSCs of molecular species of cardiolipin with mixed incorporation of 16:0, 18:1, and 18:2 acyl chains. Our data indicate a crucial role of FA elongation and alteration in cardiolipin acyl chain composition in PCSCs, representing attractive therapeutic targets in PDAC.

胰腺癌干细胞 (PCSCs) 在胰腺导管腺癌 (PDAC) 的侵袭性中起关键作用；然而，对它们的信号传导和代谢途径知之甚少。在这里，我们表明 PCSC 具有特定且常见的蛋白质组和脂质组调节。PCSC 显示出乳酸脱氢酶 A 链的下调和三功能酶亚基 α 的上调。PCSCs 上调的蛋白质主要参与脂肪酸 (FA) 延伸和不饱和脂肪酸的生物合成。因此，脂质组学揭示了长链和超长链不饱和脂肪酸的增加，这些脂肪酸是被预测为关键基因的脂肪酸延长酶 5 的产物。此外，脂质组学显示在 PCSCs 中，心磷脂分子种类的诱导与 16:0、18:1 和 18:2 酰基链的混合掺入。