AMMF’s Virtual 2021 European Cholangiocarcinoma Conference

Abstract No 1

Wnt signalling regulates metastatic cholangiocarcinoma

Dr Sarah Koushyar, Dr Valerie Meniel and Dr Toby Phesse
European Cancer Stem Cell Research Institute, Cardiff University


Cholangiocarcinoma (CC) is described as clinically silent, thus is usually diagnosed at a late stage leading to an abysmal prognosis [1].  As most patients present with advanced metastatic disease, therapeutic interventions are limited [1].

Wnt signalling has been well documented to regulate several stages of the metastatic cascade [2], and is deregulated in CC [3]. We sought to investigate this pathway in metastatic CC and explore the therapeutic benefit of targeting the Wnt pathway as a novel strategy for treating metastatic CC.


We hypothesise that Wnt signalling orchestrates several stages of the metastatic cascade of CC through FZD7, by regulating migration of CC cells, and controlling the interaction of CC cells at secondary metastatic niches.  Thus, targeting the Wnt signalling pathway at the level of the receptor/ligand interaction will be an innovative therapeutic strategy for metastatic CC.

Results and conclusion

In vitro data suggests inhibition of the Wnt pathway at the ligand/receptor interaction (via Fzd7 shRNA and inhibition of Wnt ligand release using LGK974) can decrease the metastatic potential of CC cells, stemness and canonical Wnt signalling. In vivo analysis shows that LGK974 treatment significantly reduces peritoneal metastases and liver metastases. These data  suggest that Wnt signalling can be therapeutically exploited to inhibit metastatic CC.

  1. Anderson, C.; Kim, R., Adjuvant therapy for resected extrahepatic cholangiocarcinoma: a review of the literature and future directions. Cancer Treat Rev 2009, 35, (4), 322-7.
  2. T Zhan; Rindtorff, N.; Boutros, M., Wnt signalling in cancer. Oncogene 2016, 36, 1461-1473.
  3. Boulter, L.; Guest, R. V.; Kendall, T. J.; Wilson, D. H.; Wojtacha, D.; Robson, A. J.; Ridgway, R. A.; Samuel, K.; Van Rooijen, N.; Barry, S. T.; Wigmore, S. J.; Sansom, O. J.; Forbes, S. J., WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited. J Clin Invest 2015, 125, (3), 1269-1285.

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