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.

• Authors: Xue Zeng, Hong Guo, Zhuang Liu, Zilan Qin, Yuyang Cong, Naihan Ren, Yuxiang Zhang, Na Zhang
• Journal: Cell death & disease (Cell Death Dis) Vol. 13 Issue 6 Pg. 568 (06 25 2022) ISSN: 2041-4889 [Electronic] England
• PMID: 35752610 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• S100 Proteins
• S100A11 protein, human
• Histone-Lysine N-Methyltransferase
• SMYD3 protein, human
• Transketolase

Topics

• Carcinoma, Pancreatic Ductal (pathology)
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Gene Expression Regulation, Neoplastic
• Histone-Lysine N-Methyltransferase (metabolism)
• Humans
• Pancreatic Neoplasms (pathology)
• Pentose Phosphate Pathway
• S100 Proteins (genetics, metabolism)
• Transketolase (genetics, metabolism)