Pancreatic ductal adenocarcinoma (PDAC) is one of the most refractory malignancies and has a poor prognosis. In recent years, increasing evidence has shown that an imbalance of metabolism may contribute to unrestricted pancreatic tumour progression and that the pentose phosphate pathway (PPP) plays a pivotal role in cellular metabolism. S100A11 has been shown to regulate multiple biological functions related to the progression and metastasis of various cancer types. However, the exact mechanisms and prognostic value of S100A11 in PDAC remain unclear. Here, we found that S100A11 expression was increased in PDAC and significantly associated with worse prognosis and disease progression. Mechanistically, S100A11 knockdown suppressed the PPP by impairing nascent mRNA synthesis of TKT (transketolase). The current study also demonstrated that H3K4me3 at the −268/+77 region of the TKT promoter was required for its transcriptional activation and S100A11 promoted H3K4me3 loading to the TKT promoter by interacting with SMYD3 protein. Taking these findings together, this study provided new insights into the potential value of S100A11 for treating pancreatic cancer, suggesting that it could be a therapeutic target for PDAC patients.

胰腺导管腺癌（PDAC）是最难治的恶性肿瘤之一，预后较差。近年来，越来越多的证据表明，代谢失衡可能导致胰腺肿瘤不受限制的进展，而磷酸戊糖途径（PPP）在细胞代谢中发挥着关键作用。 S100A11 已被证明可以调节与各种癌症类型的进展和转移相关的多种生物学功能。然而，S100A11 在 PDAC 中的确切机制和预后价值仍不清楚。在这里，我们发现 PDAC 中 S100A11 表达增加，并且与较差的预后和疾病进展显着相关。从机制上讲，S100A11 敲低通过损害 TKT（转酮醇酶）的新生 mRNA 合成来抑制 PPP。目前的研究还表明， TKT启动子-268/+77区域的H3K4me3是其转录激活所必需的，并且S100A11通过与SMYD3蛋白相互作用促进H3K4me3装载到TKT启动子。综合这些发现，这项研究为 S100A11 治疗胰腺癌的潜在价值提供了新的见解，表明它可能成为 PDAC 患者的治疗靶点。