Reduced Cx43 Gap Junction Plaque Expression Differentiates Thyroid Carcinomas From Benign Disease

Darr, E. Ashlie; Patel, Amit K.; Yu, Guo-Pei; Komorowski, Zbigniew; McCormick, Steven A.; Tiwari, Raj K.; Schantz, Stimson P.; Geliebter, Jan

doi:10.1001/archoto.2011.186

Cited by 8 publications

(3 citation statements)

References 19 publications

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“…It may be mediated through the Wnt signaling pathway, which has been shown for HT29 colorectal cancer cells [87] and for cells of non-tumorigenic breast epithelium HMT-3522 S1 [40]. Loss of connexin-43 may also drive malignant transformation, which was reported for benign thyroid tumors [88].…”

Section: Discussionmentioning

confidence: 86%

Comparative Analysis of Cell–Cell Contact Abundance in Ovarian Carcinoma Cells Cultured in Two- and Three-Dimensional In Vitro Models

Kutova

Sencha

Pospelov

et al. 2020

Biology

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Tumor resistance to therapy is associated with the 3D organization and peculiarities of the tumor microenvironment, of which intercellular adhesion is a key participant. In this work, the abundance of contact proteins was compared in SKOV-3 and SKOV-3.ip human ovarian adenocarcinoma cell lines, cultivated in monolayers, tumor spheroids and collagen hydrogels. Three-dimensional models were characterized by extremely low expression of basic molecules of adherens junctions E-cadherin and demonstrated a simultaneous decrease in desmosomal protein desmoglein-2, gap junction protein connexin-43 and tight junction proteins occludin and ZO-1. The reduction in the level of contact proteins was most pronounced in collagen hydrogel, accompanied by significantly increased resistance to treatment with doxorubicin and targeted anticancer toxin DARPin-LoPE. Thus, we suggest that 3D models of ovarian cancer, especially matrix-based models, tend to recapitulate tumor microenvironment and treatment responsiveness to a greater extent than monolayer culture, so they can be used as a highly relevant platform for drug efficiency evaluation.

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Section: Discussionmentioning

confidence: 86%

Comparative Analysis of Cell–Cell Contact Abundance in Ovarian Carcinoma Cells Cultured in Two- and Three-Dimensional In Vitro Models

Kutova

Sencha

Pospelov

et al. 2020

Biology

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“…Although TSH and thyroid hormones have been reported to regulate connexins in a variety of target tissues [142][143][144], their role in mediating thyroid function itself is not welldocumented. Indeed, connexin expression in the thyroid gland mainly controls cell differentiation and gland development, and most studies have been focused on the role of connexins in pathological situations [145][146][147].…”

Section: Thyroid and Parathyroid Glandsmentioning

confidence: 99%

Roles of connexins and pannexins in (neuro)endocrine physiology

Hodson

Legros

Desarménien

et al. 2015

Cell. Mol. Life Sci.

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To ensure appropriate secretion in response to demand, (neuro)endocrine tissues liberate massive quantities of hormones, which act to coordinate and synchronize biological signals in distant secretory and nonsecretory cell populations. Intercellular communication plays a central role in this control. With regard to molecular identity, junctional cell-cell communication is supported by connexin-based gap junctions. In addition, connexin hemichannels, the structural precursors of gap junctions, as well as pannexin channels have recently emerged as possible modulators of the secretory process. This review focuses on the expression of connexins and pannexins in various (neuro)endocrine tissues, including the adrenal cortex and medulla, the anterior pituitary, the endocrine hypothalamus and the pineal, thyroid and parathyroid glands. Upon a physiological or pathological stimulus, junctional intercellular coupling can be acutely modulated or persistently remodeled, thus offering multiple regulatory possibilities. The functional roles of gap junction-mediated intercellular communication in endocrine physiology as well as the involvement of connexin/pannexin-related hemichannels are also discussed.

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“…It has been shown that TSH and TH regulate the expression of connexins in a variety of target tissues, including the thyroid gland [159]. Reduced connexin-43 expression in the thyroid tissue differentiates TCA from a benign disease and provides clinical utility as a marker for malignancy [160,161], while decreased connexin-43 protein abundance in the cardiac tissue in the experimental hyperthyroid setting increases the propensity to AF and VF [26,27,108,162]. On the other hand, the upregulation of atrial connexin-40 precedes AF as well [163].…”

Section: Of 19mentioning

confidence: 99%

Pro-Arrhythmic Signaling of Thyroid Hormones and Its Relevance in Subclinical Hyperthyroidism

Tribulová

Kurahara

Hlivák

et al. 2020

IJMS

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A perennial task is to prevent the occurrence and/or recurrence of most frequent or life-threatening cardiac arrhythmias such as atrial fibrillation (AF) and ventricular fibrillation (VF). VF may be lethal in cases without an implantable cardioverter defibrillator or with failure of this device. Incidences of AF, even the asymptomatic ones, jeopardize the patient’s life due to its complication, notably the high risk of embolic stroke. Therefore, there has been a growing interest in subclinical AF screening and searching for novel electrophysiological and molecular markers. Considering the worldwide increase in cases of thyroid dysfunction and diseases, including thyroid carcinoma, we aimed to explore the implication of thyroid hormones in pro-arrhythmic signaling in the pathophysiological setting. The present review provides updated information about the impact of altered thyroid status on both the occurrence and recurrence of cardiac arrhythmias, predominantly AF. Moreover, it emphasizes the importance of both thyroid status monitoring and AF screening in the general population, as well as in patients with thyroid dysfunction and malignancies. Real-world data on early AF identification in relation to thyroid function are scarce. Even though symptomatic AF is rare in patients with thyroid malignancies, who are under thyroid suppressive therapy, clinicians should be aware of potential interaction with asymptomatic AF. It may prevent adverse consequences and improve the quality of life. This issue may be challenging for an updated registry of AF in clinical practice. Thyroid hormones should be considered a biomarker for cardiac arrhythmias screening and their tailored management because of their multifaceted cellular actions.

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Reduced Cx43 Gap Junction Plaque Expression Differentiates Thyroid Carcinomas From Benign Disease

Abstract: Our data provide evidence that the absence of Cx43 plaque staining is associated with thyroid cancer and thus holds potential clinical utility as a marker for malignant disease.

Cited by 8 publications

References 19 publications

Comparative Analysis of Cell–Cell Contact Abundance in Ovarian Carcinoma Cells Cultured in Two- and Three-Dimensional In Vitro Models

Comparative Analysis of Cell–Cell Contact Abundance in Ovarian Carcinoma Cells Cultured in Two- and Three-Dimensional In Vitro Models

Roles of connexins and pannexins in (neuro)endocrine physiology

Pro-Arrhythmic Signaling of Thyroid Hormones and Its Relevance in Subclinical Hyperthyroidism

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