Dataset Information

S100A11 activates the pentose phosphate pathway to induce malignant biological behaviour of pancreatic ductal adenocarcinoma.

ABSTRACT: 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.

SUBMITTER: Zeng X

PROVIDER: S-EPMC9233679 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

S100A11 activates the pentose phosphate pathway to induce malignant biological behaviour of pancreatic ductal adenocarcinoma.

Zeng Xue X Guo Hong H Liu Zhuang Z Qin Zilan Z Cong Yuyang Y Ren Naihan N Zhang Yuxiang Y Zhang Na N

Cell death & disease 20220625 6

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 ...[more]

PMID: 35752610

Similar Datasets

Project description:Obesity is a risk factor for pancreatic ductal adenocarcinoma (PDAC), but it is not clear how obesity contributes to pancreatic carcinogenesis. The oncogenic form of KRAS is expressed during early stages of PDAC development and is detected in almost all of these tumors. However, there is evidence that mutant KRAS requires an additional stimulus to activate its full oncogenic activity and that this stimulus involves the inflammatory response. We investigated whether the inflammation induced by a high-fat diet, and the accompanying up-regulation of cyclooxygenase-2 (COX2), increases Kras activity during pancreatic carcinogenesis in mice.We studied mice with acinar cell-specific expression of KrasG12D (LSL-Kras/Ela-CreERT mice) alone or crossed with COX2 conditional knockout mice (COXKO/LSL-Kras/Ela-CreERT). We also studied LSL-Kras/PDX1-Cre mice. All mice were fed isocaloric diets with different amounts of fat, and a COX2 inhibitor was administered to some LSL-Kras/Ela-CreERT mice. Pancreata were collected from mice and analyzed for Kras activity, levels of phosphorylated extracellular-regulated kinase, inflammation, fibrosis, pancreatic intraepithelial neoplasia (PanIN), and PDACs.Pancreatic tissues from LSL-Kras/Ela-CreERT mice fed high-fat diets (HFDs) had increased Kras activity, fibrotic stroma, and numbers of PanINs and PDACs than LSL-Kras/Ela-CreERT mice fed control diets; the mice fed the HFDs also had shorter survival times than mice fed control diets. Administration of a COX2 inhibitor to LSL-Kras/Ela-CreERT mice prevented these effects of HFDs. We also observed a significant reduction in survival times of mice fed HFDs. COXKO/LSL-Kras/Ela-CreERT mice fed HFDs had no evidence for increased numbers of PanIN lesions, inflammation, or fibrosis, as opposed to the increases observed in LSL-Kras/Ela-CreERT mice fed HFDs.In mice, an HFD can activate oncogenic Kras via COX2, leading to pancreatic inflammation and fibrosis and development of PanINs and PDAC. This mechanism might be involved in the association between risk for PDAC and HFDs.

Dataset Information

S100A11 activates the pentose phosphate pathway to induce malignant biological behaviour of pancreatic ductal adenocarcinoma.

Publications

S100A11 activates the pentose phosphate pathway to induce malignant biological behaviour of pancreatic ductal adenocarcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets