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This research was supported by funding from Qatar Foundation to Weill Cornell Medicine in Qatar through the BMRP2 Grant.
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Aleksic, JovanaAuthorIdentifying novel interactions of the colon-cancer related APC protein with Wnt-pathway nuclear transcription factors
Publicated to:Cancer Cell International. 22 (1): 376- - 2022-12-01 22(1), DOI: 10.1186/s12935-022-02799-1
Authors: Al-Thani, Nayra M; Schaefer-Ramadan, Stephanie; Aleksic, Jovana; Mohamoud, Yasmin A; Malek, Joel A
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Abstract
BackgroundColon cancer is often driven by mutations of the adenomatous polyposis coli (APC) gene, an essential tumor suppressor gene of the Wnt beta-catenin signaling pathway. APC and its cytoplasmic interactions have been well studied. However, various groups have also observed its presence in the nucleus. Identifying novel interactions of APC in the Wnt pathway will provide an opportunity to understand APC's nuclear role better and ultimately identify potential cancer treatment targets. MethodsWe used the all-vs-all sequencing (AVA-Seq) method to interrogate the interactome of protein fragments spanning most of the 60 Wnt beta-catenin pathway proteins. Using protein fragments identified the interacting regions between the proteins with more resolution than a full-length protein approach. Pull-down assays were used to validate a subset of these interactions. Results74 known and 703 novel Wnt beta-catenin pathway protein-protein interactions were recovered in this study. There were 8 known and 31 novel APC protein-protein interactions. Novel interactions of APC and nuclear transcription factors TCF7, JUN, FOSL1, and SOX17 were particularly interesting and confirmed in validation assays. ConclusionBased on our findings of novel interactions between APC and transcription factors and previous evidence of APC localizing to the nucleus, we suggest APC may compete and repress CTNNB1. This would occur through APC binding to the transcription factors (JUN, FOSL1, TCF7) to regulate the Wnt signaling pathway including through enhanced marking of CTNNB1 for degradation in the nucleus by APC binding with SOX17. Additional novel Wnt beta-catenin pathway protein-protein interactions from this study could lead researchers to novel drug designs for cancer.
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Bibliometric impact. Analysis of the contribution and dissemination channel
The work has been published in the journal Cancer Cell International due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position 59/241, thus managing to position itself as a Q1 (Primer Cuartil), in the category Oncology.
From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 1.51, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jun 2025)
Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-06-07, the following number of citations:
- WoS: 2
- Scopus: 2
- Europe PMC: 1
- OpenCitations: 3
Impact and social visibility
Leadership analysis of institutional authors
This work has been carried out with international collaboration, specifically with researchers from: Qatar.