ABSTRACT
Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the family of non-inhibitory serpins. The broad spectrum of PEDF biological activity is evident when considering its effects in promoting cell survival and proliferation, as well as its antiangiogenic, antitumor, and anti-metastatic properties. Although the structural domains of the PEDF gene that mediate such diverse effects and their mechanisms of action have not been completely elucidated, there is a large body of evidence describing their diverse range of activities; this evidence combined with the regulation of PEDF expression by sex steroids and their receptors have led to the idea that PEDF is not only a diagnostic and prognostic marker for certain diseases such as cancer, but is also a potential therapeutic target. In this manner, this paper aims to generally review the regulation of PEDF expression and PEDF interactions, as well as the findings that relate PEDF to the role of estrogens and estrogen receptors. In addition, this manuscript will review major advances toward potential therapeutic applications of PEDF.
ABSTRACT
The epithelial-mesenchymal transition (EMT) is a biological phenomenon responsible for the formation of different tissues and organs during normal metazoan development. Because of the connection of the EMT with the pathogenesis of certain diseases, such as cancer, the attention of the scientific community has been directed towards the search for and identification of effective therapeutic targets. These targets include signal transduction in cancerous stem cells and the use of microRNAs, which would inhibit EMT-associated phenotypic changes and tumoral progression. In an attempt to compile relevant and current information, this work addresses concepts that define the EMT and the advances in this field. The wealth of knowledge gained from areas such as the loss of cell polarity and intracellular adhesion complexes, the signaling pathways implicated, microRNA participation in this process, and stemness acquisition in embryonic and cancerous cells, all of which allow for the visualization of promising perspectives, particularly, methods for targeting advanced malignancies, are presented herein.
Subject(s)
Antineoplastic Agents/pharmacology , Epithelial-Mesenchymal Transition , Molecular Targeted Therapy , Neoplasms/therapy , Animals , Antineoplastic Agents/therapeutic use , Cell Adhesion , Cell Adhesion Molecules/physiology , Cell Differentiation , Cell Movement , Cell Polarity , Cell Transformation, Neoplastic , Disease Progression , Embryonic Development , Epithelial-Mesenchymal Transition/drug effects , Epithelial-Mesenchymal Transition/physiology , Fibrosis , Humans , Intracellular Signaling Peptides and Proteins/physiology , MicroRNAs/physiology , Neoplasm Proteins/physiology , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/pathology , RNA, Neoplasm/physiology , Signal Transduction/drug effects , Signal Transduction/physiologyABSTRACT
The epithelial-mesenchymal transition (EMT) is a biological phenomenon responsible for the formation of different tissues and organs during normal metazoan development. Because of the connection of the EMT with the pathogenesis of certain diseases, such as cancer, the attention of the scientific community has been directed towards the search for and identification of effective therapeutic targets. These targets include signal transduction in cancerous stem cells and the use of microRNAs, which would inhibit EMT-associated phenotypic changes and tumoral progression. In an attempt to compile relevant and current information, this work addresses concepts that define the EMT and the advances in this field. The wealth of knowledge gained from areas such as the loss of cell polarity and intracellular adhesion complexes, the signaling pathways implicated, microRNA participation in this process, and stemness acquisition in embryonic and cancerous cells, all of which allow for the visualization of promising perspectives, particularly, methods for targeting advanced malignancies, are presented herein.
La transición epitelio-mesenquimática (TEM) es el fenómeno biológico responsable de la formación de los diferentes tejidos y órganos durante el desarrollo normal de los organismos metazoarios. En razón de su conexión con la patogénesis de ciertas enfermedades como el cáncer, la atención de la comunidad científica se ha redireccionado hacia la búsqueda e identificación de blancos terapéuticos efectivos, como la transducción de señales de las células madre cancerosas o la utilización de microARNs, que permitirían bloquear los cambios fenotípicos asociados con la TEM y, por ende, la progresión tumoral. En un intento por recopilar información relevante y actualizada, el presente trabajo aborda conceptos que definen a la TEM y avances alcanzados en este campo. El acervo de conocimiento obtenido en aspectos como pérdida de la polaridad celular y de los complejos de adhesión intercelular, vías de señalización implicadas y participación de los microARNs en el proceso, así como adquisición de stemness o troncalidad, tanto en células embrionarias como cancerosas, hace posible visualizar perspectivas promisorias, en especial en lo que se refiere a las terapias contra las malignidades de alto grado.
