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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, JovanaAutor o CoautorIdentifying novel interactions of the colon-cancer related APC protein with Wnt-pathway nuclear transcription factors
Publicado en:Cancer Cell International. 22 (1): 376- - 2022-12-01 22(1), DOI: 10.1186/s12935-022-02799-1
Autores: Al-Thani, Nayra M; Schaefer-Ramadan, Stephanie; Aleksic, Jovana; Mohamoud, Yasmin A; Malek, Joel A
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Resumen
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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Impacto bibliométrico. Análisis de la aportación y canal de difusión
El trabajo ha sido publicado en la revista Cancer Cell International debido a la progresión y el buen impacto que ha alcanzado en los últimos años, según la agencia WoS (JCR), se ha convertido en una referencia en su campo. En el año de publicación del trabajo, 2022, se encontraba en la posición 59/241, consiguiendo con ello situarse como revista Q1 (Primer Cuartil), en la categoría Oncology.
Desde una perspectiva relativa, y atendiendo al indicador del impacto normalizado calculado a partir del Field Citation Ratio (FCR) de la fuente Dimensions, arroja un valor de: 1.52, lo que indica que, de manera comparada con trabajos en la misma disciplina y en el mismo año de publicación, lo ubica como trabajo citado por encima de la media. (fuente consultada: Dimensions May 2025)
De manera concreta y atendiendo a las diferentes agencias de indexación, el trabajo ha acumulado, hasta la fecha 2025-05-31, el siguiente número de citas:
- WoS: 2
- Scopus: 2
- Europe PMC: 1
- OpenCitations: 3
Impacto y visibilidad social
Análisis de liderazgo de los autores institucionales
Este trabajo se ha realizado con colaboración internacional, concretamente con investigadores de: Qatar.