2. Academic Validation
  3. ALDOA inhibits cell cycle arrest induced by DNA damage via the ATM-PLK1 pathway in pancreatic cancer cells

ALDOA inhibits cell cycle arrest induced by DNA damage via the ATM-PLK1 pathway in pancreatic cancer cells

  • Cancer Cell Int. 2021 Sep 26;21(1):514. doi: 10.1186/s12935-021-02210-5.
Haidi Chen  # 1 2 3 4,  Zeng Ye  # 1 2 3 4,  Xiaowu Xu  # 1 2 3 4,  Yi Qin 1 2 3 4,  Changfeng Song 1 2 3 4,  Guixiong Fan 1 2 3 4,  Haifeng Hu 1 2 3 4,  Yuheng Hu 1 2 3 4,  Xianjun Yu 1 2 3 4,  Wensheng Liu 5 6 7 8,  Shunrong Ji 9 10 11 12,  Wenyan Xu 13 14 15 16
Affiliations

Affiliations

  • 1 Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 Dong'An Road, Shanghai, China.
  • 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
  • 3 Shanghai Pancreatic Cancer Institute, No. 270 Dong'An Road, Shanghai, 200032, China.
  • 4 Pancreatic Cancer Institute, Fudan University, Shanghai, China.
  • 5 Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 Dong'An Road, Shanghai, China. [email protected].
  • 6 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. [email protected].
  • 7 Shanghai Pancreatic Cancer Institute, No. 270 Dong'An Road, Shanghai, 200032, China. [email protected].
  • 8 Pancreatic Cancer Institute, Fudan University, Shanghai, China. [email protected].
  • 9 Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 Dong'An Road, Shanghai, China. [email protected].
  • 10 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. [email protected].
  • 11 Shanghai Pancreatic Cancer Institute, No. 270 Dong'An Road, Shanghai, 200032, China. [email protected].
  • 12 Pancreatic Cancer Institute, Fudan University, Shanghai, China. [email protected].
  • 13 Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 Dong'An Road, Shanghai, China. [email protected].
  • 14 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. [email protected].
  • 15 Shanghai Pancreatic Cancer Institute, No. 270 Dong'An Road, Shanghai, 200032, China. [email protected].
  • 16 Pancreatic Cancer Institute, Fudan University, Shanghai, China. [email protected].
  • # Contributed equally.
PMID: 34565365 DOI: 10.1186/s12935-021-02210-5
Abstract

Background: ALDOA is a glycolytic Enzyme found mainly in developing embryos, adult muscle and various malignant tumours, including pancreatic tumours. Our previous study revealed that ALDOA, an oncogene, can promote the proliferation and metastasis of pancreatic tumours. Furthermore, ALDOA could predict poor prognosis in patients with pancreatic tumours.

Methods: IHC analysis of PDAC tissues was conducted. Western blotting, PCR, cellular IF experiments and cell cycle assessment were conducted utilizing cell lines. GSEA and KEGG pathway analysis were used to identify potential downstream pathways.

Results: To explore the effects of ALDOA on the occurrence and development of pancreatic tumours, we analysed the RNA sequencing results and found that ALDOA could inhibit the DDR. Under normal circumstances, when DNA is damaged, initiation of the DDR causes cell cycle arrest, DNA repair or cell Apoptosis. Further experiments showed that ALDOA could inhibit DNA repair and reverse cell cycle arrest induced by DNA damage so that DNA damage persisted to promote the occurrence and progression of Cancer.

Conclusions: Regarding the molecular mechanism, we found that ALDOA inhibited the DDR and improved activation of the cell cycle checkpoint PLK1 by suppressing ATM, which promotes tumour cell progression. Consequently, ALDOA has a profound effect on pancreatic Cancer development.

Keywords

ALDOA; ATM; Cell cycle arrest; PLK1; Pancreatic cancer.

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