MUC1 is responsible for the pro-metastatic potential of calycosin in pancreatic ductal adenocarcinoma

Wenqing Chen, Zhu Zhang, Kin Lam Yung*, Joshua Ko*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review


Pancreatic ductal adenocarcinoma (PDAC) is a prominent type of pancreatic cancer. We have recently unveiled that the anti-tumor adjuvant calycosin concurrently possesses growth-inhibitory and pro-metastatic potential in PDAC development by regulating transforming growth factor β (TGF-β), which plays dual roles as both tumor suppressor and tumor promoter. Hence, we are interested to explore if the pro-metastatic property of the drug could be attenuated for effective treatment of PDAC. Through network pharmacology, MUC1 had been identified as the most common drug target of herbal Astragalus constituents (including calycosin) in treating PDAC. Following MUC1 gene silencing, the drug effects of calycosin on migratory activity, growth and metabolic regulation of PDAC cells were assessed by using immunofluorescence microscopy, quantitative real-time polymerase chain reaction (qRT-PCR), Western immunoblotting, co-immunoprecipitation (Co-IP), wound healing assay and flow cytometry, respectively. Through in vivo experiments, we further validated the working relationship between MUC1 and TGF-β. Results have elucidated that MUC1 gene suppression could switch off the migratory and pro-metastatic drive of calycosin while retaining its growth-inhibitory power by inducing apoptosis and cell cycle arrest, as well as facilitating autophagy and metabolic regulation. The underlying mechanism involves downregulation of TGF-β that acts via modulation of AMP-activated protein kinase (AMPK), Sirtuin 1 (Sirt1) and fibroblast growth factor 21 (FGF21) signaling. These findings have provided new insights in the safe and target-specific treatment of PDAC.
Original languageEnglish
Pages (from-to)3242–3258
Number of pages17
JournalAmerican Journal of Cancer Research
Issue number7
Early online date15 Jul 2022
Publication statusPublished - 30 Jul 2022

Scopus Subject Areas

  • Cancer Research

User-Defined Keywords

  • Calycosin
  • MUC1
  • pancreatic ductal adenocarcinoma
  • metastasis
  • TGF-β


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