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    Connexins in Cancer, the Possible Role of Connexin46 as a Cancer Stem Cell-Determining Protein
    (2023)
    Isidora M. León-Fuentes
    ;
    María G. Salgado-Gil
    ;
    María S. Novoa
    ;
    RETAMAL LUCERO, MAURICIO ANTONIO  
    <jats:p>Cancer is a widespread and incurable disease caused by genetic mutations, leading to uncontrolled cell proliferation and metastasis. Connexins (Cx) are transmembrane proteins that facilitate intercellular communication via hemichannels and gap junction channels. Among them, Cx46 is found mostly in the eye lens. However, in pathological conditions, Cx46 has been observed in various types of cancers, such as glioblastoma, melanoma, and breast cancer. It has been demonstrated that elevated Cx46 levels in breast cancer contribute to cellular resistance to hypoxia, and it is an enhancer of cancer aggressiveness supporting a pro-tumoral role. Accordingly, Cx46 is associated with an increase in cancer stem cell phenotype. These cells display radio- and chemoresistance, high proliferative abilities, self-renewal, and differentiation capacities. This review aims to consolidate the knowledge of the relationship between Cx46, its role in forming hemichannels and gap junctions, and its connection with cancer and cancer stem cells.</jats:p>
    Scopus© Citations 3  2
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    Connexin-46 Contained in Extracellular Vesicles Enhance Malignancy Features in Breast Cancer Cells
    (2020)
    ACUÑA ASTUDILLO, RODRIGO ANTONIO  
    ;
    Manuel Varas-Godoy
    ;
    Viviana M. Berthoud
    ;
    ALFARO CORTEZ, IVAN ESTEBAN  
    ;
    RETAMAL LUCERO, MAURICIO ANTONIO  
    <jats:p>Under normal conditions, almost all cell types communicate with their neighboring cells through gap junction channels (GJC), facilitating cellular and tissue homeostasis. A GJC is formed by the interaction of two hemichannels; each one of these hemichannels in turn is formed by six subunits of transmembrane proteins called connexins (Cx). For many years, it was believed that the loss of GJC-mediated intercellular communication was a hallmark in cancer development. However, nowadays this paradigm is changing. The connexin 46 (Cx46), which is almost exclusively expressed in the eye lens, is upregulated in human breast cancer, and is correlated with tumor growth in a Xenograft mouse model. On the other hand, extracellular vesicles (EVs) have an important role in long-distance communication under physiological conditions. In the last decade, EVs also have been recognized as key players in cancer aggressiveness. The aim of this work was to explore the involvement of Cx46 in EV-mediated intercellular communication. Here, we demonstrated for the first time, that Cx46 is contained in EVs released from breast cancer cells overexpressing Cx46 (EVs-Cx46). This EV-Cx46 facilitates the interaction between EVs and the recipient cell resulting in an increase in their migration and invasion properties. Our results suggest that EV-Cx46 could be a marker of cancer malignancy and open the possibility to consider Cx46 as a new therapeutic target in cancer treatment.</jats:p>
      3Scopus© Citations 28
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    Role of ROS/RNS in Preeclampsia: Are Connexins the Missing Piece?
    (2020)
    María F. Rozas-Villanueva
    ;
    Paola Casanello
    ;
    MAURICIO ANTONIO RETAMAL LUCERO
    <jats:p>Preeclampsia is a pregnancy complication that appears after 20 weeks of gestation and is characterized by hypertension and proteinuria, affecting both mother and offspring. The cellular and molecular mechanisms that cause the development of preeclampsia are poorly understood. An important feature of preeclampsia is an increase in oxygen and nitrogen derived free radicals (reactive oxygen species/reactive nitrogen species (ROS/RNS), which seem to be central players setting the development and progression of preeclampsia. Cell-to-cell communication may be disrupted as well. Connexins (Cxs), a family of transmembrane proteins that form hemichannels and gap junction channels (GJCs), are essential in paracrine and autocrine cell communication, allowing the movement of signaling molecules between cells as well as between the cytoplasm and the extracellular media. GJCs and hemichannels are fundamental for communication between endothelial and smooth muscle cells and, therefore, in the control of vascular contraction and relaxation. In systemic vasculature, the activity of GJCs and hemichannels is modulated by ROS and RNS. Cxs participate in the development of the placenta and are expressed in placental vasculature. However, it is unknown whether Cxs are modulated by ROS/RNS in the placenta, or whether this potential modulation contributes to the pathogenesis of preeclampsia. Our review addresses the possible role of Cxs in preeclampsia, and the plausible modulation of Cxs-formed channels by ROS and RNS. We suggest these factors may contribute to the development of preeclampsia.</jats:p>
    Scopus© Citations 18  1
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    Diseases associated with leaky hemichannels
    (2015)
    RETAMAL LUCERO, MAURICIO ANTONIO  
    ;
    Edison P. Reyes
    ;
    Isaac E. García
    ;
    Bernardo Pinto
    ;
    Agustín D. Martínez
      21Scopus© Citations 94
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    Connexinopathies: a structural and functional glimpse
    (2016)
    Isaac E. García
    ;
    Pavel Prado
    ;
    Amaury Pupo
    ;
    Oscar Jara
    ;
    Diana Rojas-Gómez
      12  1Scopus© Citations 44
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    Scopus© Citations 15  4
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    Extracellular Cysteine in Connexins: Role as Redox Sensors
    (2016)
    RETAMAL LUCERO, MAURICIO ANTONIO  
    ;
    Isaac E. García
    ;
    Bernardo I. Pinto
    ;
    Amaury Pupo
    ;
    David Báez
    Scopus© Citations 30  1
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    Scopus© Citations 13  1