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Updated: Aug 18, 2026
A Multiplexed Luciferase-based Screening Platform for Interrogating Cancer-associated Signal Transduction in Cultured Cells
Published on: July 3, 2013
High-throughput targeted screening in triple-negative breast cancer cells identifies Wnt-inhibiting activities in
Artem Blagodatski1, Vsevolod Cherepanov1,2,3, Alexey Koval3
1School of Biomedicine, Far Eastern Federal University, Vladivostok, Russian Federation.
Abstract:
Pro-proliferative oncogenic signaling is one of the hallmarks of cancer. Specific targeting of such signaling pathways is one of the main approaches to modern anti-cancer drug discovery, as opposed to more traditional search for general cytotoxic agents. Natural products, especially from marine sources, represent a largely untapped source of chemical diversity, which so far have mostly been screened for cytotoxicity. Here we present a pioneering pipeline of high-throughput screening of marine-based activities targeted against the Wnt signaling pathway, which is one of the key factors in oncogenic transformation, growth and metastasis in different cancers, including the devastating triple-negative breast cancer (TNBC) currently lacking any targeted therapies. This pipeline consisted of collection and characterization of numerous invertebrates during the SokhoBio expedition to the Kuril Basin in North Pacific, preparation of extracts from these specimen, and their screening in dedicated assays monitoring Wnt signaling in TNBC cells. This approach yielded a number of promising hits, including highly specific anti-Wnt activities targeting multiple levels within the Wnt pathway from Ophiura irrorata and other Pacific brittle stars.
Insights
Marine natural products were screened for Wnt pathway inhibitors, crucial for cancer. Promising anti-Wnt activities were identified in Pacific brittle stars, offering new therapeutic avenues for triple-negative breast cancer.
Area of Science:
- Marine biology
- Biochemistry
- Oncology
Background:
- Pro-proliferative oncogenic signaling is a key hallmark of cancer.
- Targeting specific signaling pathways is a focus of modern anti-cancer drug discovery.
- Marine natural products offer vast, largely untapped chemical diversity for drug screening.
Purpose of the Study:
- To develop and implement a high-throughput screening pipeline for marine-based compounds targeting the Wnt signaling pathway.
- To identify novel anti-cancer agents, particularly for triple-negative breast cancer (TNBC).
Main Methods:
- Collection and characterization of marine invertebrates from the Kuril Basin.
- Preparation of extracts from collected specimens.
- Screening of extracts using assays monitoring Wnt signaling in TNBC cells.
Main Results:
- Identification of a pioneering pipeline for screening marine natural products against the Wnt pathway.
- Discovery of promising hits with specific anti-Wnt activities from Pacific brittle stars (Ophiura irrorata).
- Activities were found to target multiple levels of the Wnt pathway.
Conclusions:
- Marine natural products are a valuable source for discovering targeted anti-cancer therapies.
- The identified anti-Wnt activities represent potential leads for novel treatments against TNBC and other cancers.
- This screening approach successfully identified specific inhibitors of a key oncogenic pathway.
