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      Secreted Frizzled - related Protein 4 y el cáncer de mama Translated title: Secreted Frizzled - related Protein 4 and breast càncer

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          Abstract

          Abstract Introduction: cell's correct functionality and surveillance are brokered by a wide range of essential proceedings. The delicate equilibrium required between those phenomenon means that an error in the control mechanisms provoke the carcinogenesis commencement. In those metabolic pathways in charge of controlling the mechanisms are found the Wnt signaling pathways. Therefore, molecules that interact with the pathways mentioned, where secreted Frizzled - Related Protein 4 is located, will play a key role in the pathology knowledge. Method: a bibliographic research has been done in referral databases, such as Medline and Scopus. Results: sFRP4 has been identified as a negative modulator of the Wnt signaling pathways. This is due to its capacity of competing for the Wnt ligands and avoiding the commencement of the pathways. Otherwise, sFRP4 is essential for the control of the cancer beginning and development in those tissues where the protein is expressed, being mammary tissues considered into them. Conclusions: recent studies about the implications of sFRP4 in the development of several pathologies justify that the protein had garnered attention in recent years. Furthermore, it can be affirmed that sFRP4 presents an interesting potential as biomarker in the breast cancer treatment, diagnosis and prognosis, among other pathologies.

          Translated abstract

          Resumen Introducción: el correcto funcionamiento y la supervivencia de la célula vienen mediados por multitud de procesos clave. El delicado equilibrio que se requiere entre dichos fenómenos hace que un error en los mecanismos de control desencadene el inicio de la carcinogénesis. Dentro de las rutas metabólicas encargadas de su regulación se encuentran las vías de señalización del Wnt. De esta forma, aquellas moléculas que intervengan en dichas vías presentarán un papel clave para el estudio de la patología, entre las que destaca secreted Frizzled - Related Protein 4 (sFRP4). Método: se ha llevado a cabo una búsqueda bibliográfica en bases de datos de referencia, como es el caso de Medline, Scopus o Web of Science. Resultados: a sFRP4 se le ha otorgado el papel de modulador negativo de las vías de Wnt debido a su capacidad de competir por los ligandos Wnt y evitar el inicio de dichas rutas. Por lo tanto, sFRP4 será esencial en el control del inicio y desarrollo del cáncer en aquellos tejidos donde se exprese la proteína, dentro de los que se considera el tejido mamario. Conclusiones: los recientes estudios acerca de la implicación de sFRP4 en el desarrollo de diversas patologías, justifican que la proteína haya captado la atención en los últimos años. De esta forma, se puede afirmar que sFRP4 presenta un interesante potencial como biomarcador en el tratamiento, diagnóstico y pronóstico del cáncer de mama, entre otras enfermedades.

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          Most cited references63

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          Dishevelled: The hub of Wnt signaling.

          Wnt signaling controls a variety of developmental and homeostatic events. As a key component of Wnt signaling, Dishevelled (Dvl/Dsh) protein relays Wnt signals from receptors to downstream effectors. In the canonical Wnt pathway that depends on the nuclear translocation of beta-catenin, Dvl is recruited by the receptor Frizzled and prevents the constitutive destruction of cytosolic beta-catenin. In the non-canonical Wnt pathways such as Wnt-Frizzled/PCP (planar cell polarity) signaling, Dvl signals via the Daam1-RhoA axis and the Rac1 axis. In addition, Dvl plays important roles in Wnt-GSK3beta-microtubule signaling, Wnt-calcium signaling, Wnt-RYK signaling, Wnt-atypical PKC signaling, etc. Dvl also functions to mediate receptor endocytosis. To fulfill its multifaceted functions, it is not surprising that Dvl associates with various kinds of proteins. Its activity is also modulated dynamically by phosphorylation, ubiquitination and degradation. In this review, we summarize the current understanding of Dvl functions in Wnt signal transduction and its biological functions in mouse development, and also discuss the molecular mechanisms of its actions. 2009 Elsevier Inc. All rights reserved.
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            Wnt signaling in development and tissue homeostasis.

            The Wnt-β-catenin signaling pathway is an evolutionarily conserved cell-cell communication system that is important for stem cell renewal, cell proliferation and cell differentiation both during embryogenesis and during adult tissue homeostasis. Genetic or epigenetic events leading to hypo- or hyper-activation of the Wnt-β-catenin signaling cascade have also been associated with human diseases such as cancer. Understanding how this pathway functions is thus integral for developing therapies to treat diseases or for regenerative medicine approaches. Here, and in the accompanying poster, we provide an overview of Wnt-β-catenin signaling and briefly highlight its key functions during development and adult tissue homeostasis.
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              The Wnt signaling pathway in cancer.

              The Wnt signaling pathway is critically involved in both the development and homeostasis of tissues via regulation of their endogenous stem cells. Aberrant Wnt signaling has been described as a key player in the initiation of and/or maintenance and development of many cancers, via affecting the behavior of Cancer Stem Cells (CSCs). CSCs are considered by most to be responsible for establishment of the tumor and also for disease relapse, as they possess inherent drug-resistance properties. The development of new therapeutic compounds targeting the Wnt signaling pathway promises new hope to eliminate CSCs and achieve cancer eradication. However, a major challenge resides in developing a strategy efficient enough to target the dysregulated Wnt pathway in CSCs, while being safe enough to not damage the normal somatic stem cell population required for tissue homeostasis and repair. Here we review recent therapeutic approaches to target the Wnt pathway and their clinical applications.
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                Author and article information

                Journal
                ars
                Ars Pharmaceutica (Internet)
                Ars Pharm
                Universidad de Granada (Granada, Granada, Spain )
                2340-9894
                December 2021
                : 62
                : 4
                : 438-450
                Affiliations
                [1] Granada Andalucía orgnameUniversidad de Granada orgdiv1Facultad de Farmacia orgdiv2Departamento de Bioquímica y Biología Molecular II Spain
                [2] Armilla Andalucía orgnameUniversidad de Granada orgdiv1Centro de Investigaciones Biomédicas (CIBM) orgdiv2Instituto de Nutrición y Tecnología de los Alimentos "José Mataix" (INYTA) Spain
                Article
                S2340-98942021000400438 S2340-9894(21)06200400438
                10.30827/ars.v62i4.21740
                3a9bf6cd-34f9-4546-8a77-4a6331f22229

                This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

                History
                : 03 September 2021
                : 08 July 2021
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 63, Pages: 13
                Product

                SciELO Spain

                Categories
                Review Articles

                canónica,β - catenina,sFRP4,breast cancer,Frizzled,non - canonical,canonical,β - catenin,cáncer de mama,no canónica

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