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This research was supported by funding from Qatar Foundation to Weill Cornell Medicine in Qatar through the BMRP2 Grant.

Analysis of institutional authors

Aleksic, JovanaAuthor

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Identifying 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.

Keywords

Adenomatous polyposis coliAdenomatous polyposis-coliApcBeta-cateninC-junCancerCell-cycle progressionCreb binding-proteinGene promoteGsk-3-beta-dependent phosphorylationNovel protein interactionPpiPpisProtein interactionsSignaling pathwayTranscription factorsTumor-suppressorWnt signaling pathwayWnt/beta-catenin

Quality index

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

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-06-07:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 10.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 10 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 11.6.
  • The number of mentions on the social network Facebook: 1 (Altmetric).
  • The number of mentions on the social network X (formerly Twitter): 2 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Qatar.