Connexin 43 (Cx43) Expression in Laryngeal Squamous Cell Carcinomas: Preliminary Data on Its Possible Prognostic Role

Puzzo, Lidia; Caltabiano, Rosario; Parenti, Rosalba; Trapasso, Serena; Allegra, Eugenia

doi:10.1007/s12105-016-0685-x

Cited by 17 publications

(9 citation statements)

References 21 publications

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“…In our previous study, we found that Cx43 could be regarded as a prognostic factor in head and neck cancers, and the reduction of its expression level is associated with a significantly poorer prognosis [14]. This was confirmed by Puzzo et al in laryngeal cancers [24]. However, other studies found inverse association between Cx43 expression and overall survival suggesting, that Cx43 has different role in certain tumor types (esophageal, oropharyngeal) or localization (cytoplasm and nucleus vs. membrane) [25][26][27].…”

Section: Discussionsupporting

confidence: 61%

The Potential Impact of Connexin 43 Expression on Bcl-2 Protein Level and Taxane Sensitivity in Head and Neck Cancers–In Vitro Studies

Gurbi

Brauswetter

Varga

et al. 2019

Cancers

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The poor prognosis of head and neck squamous cell carcinoma (HNSCC) is partly due to the lack of reliable predictive markers. Connexin 43 (Cx43) protein and its cell-communication channels have been assigned tumor suppressor functions while the anti-apoptotic Bcl-2 (B-cell lymphoma-2) protein has been associated with negative prognostic significance in cancer. This study aimed to test the role of Cx43 protein on Bcl-2 expression, tumor progression and response to taxane-based treatment in HNSCC. Human papillomavirus (HPV) negative HNSCC cell lines were tested for paclitaxel sensitivity through measuring apoptosis induction, cell viability and changes in Cx43 and Bcl-2 levels using flow cytometry, cell viability assay, immunocytochemistry and western blot. Inhibition of Cx43 expression using siRNA increased Bcl-2 protein levels in SCC25 (tongue squamous cell carcinoma) cells, while forced Cx43 expression reduced Bcl-2 levels and supported paclitaxel cytotoxicity in FaDu (hypopharynx squamous cell carcinoma) cells. In vitro results were in line with protein expression and clinicopathological features tested in tissue microarray samples of HNSCC patients. Our data demonstrate that elevated Cx43 and reduced Bcl-2 levels may indicate HNSCC sensitivity to taxane-based treatments. On the contrary, silencing of the Cx43 gene GJA1 (gap junction protein alpha-1) can result in increased Bcl-2 expression and reduced paclitaxel efficiency. Clinical tumor-based analysis also confirmed the inverse correlation between Cx43 and Bcl-2 expression.

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Section: Discussionsupporting

confidence: 61%

The Potential Impact of Connexin 43 Expression on Bcl-2 Protein Level and Taxane Sensitivity in Head and Neck Cancers–In Vitro Studies

Gurbi

Brauswetter

Varga

et al. 2019

Cancers

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“…In certain tumors where Cx43 is detected at the cell surface, the levels of Cx43 were reversely correlated with lymph node metastasis and prognosis [38, 39] (Table 1). The above studies suggested the inhibitory roles of Cx43 in tumorigenesis.…”

Section: Connexin 43mentioning

confidence: 99%

Emerging roles of gap junction proteins connexins in cancer metastasis, chemoresistance and clinical application

Wang

2019

J Biomed Sci

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Connexin, a four-pass transmembrane protein, contributes to assembly of gap junctions among neighboring cells and thus facilitates gap junctional intercellular communication (GJIC). Traditionally, the roles of connexins were thought to mediate formation of hemichannels and GJIC assembly for transportation of ions and small molecules. Many studies have observed loss of GJIC, due to reduced expression or altered cytoplasmic localization of connexins, in primary tumor cells. Connexins are generally considered tumor-suppressive. However, recent studies of clinical samples suggested a different role of connexins in that expression levels and membrane localization of connexins, including Connexin 43 (Cx43, GJA1) and Connexin 26 (Cx26, GJB2), were found to be enhanced in metastatic lesions of cancer patients. Cx43- and Cx26-mediated GJIC was found to promote cancer cell migration and adhesion to the pulmonary endothelium. Regulatory circuits involved in the induction of connexins and their functional effects have also been reported in various types of cancer. Connexins expressed in stromal cells were correlated with metastasis and were implicated in regulating metastatic behaviors of cancer cells. Recent studies have revealed that connexins can contribute to cellular phenotypes via multiple ways, namely 1) GJIC, 2) C-terminal tail-mediated signaling, and 3) cell-cell adhesion during gap junction formation. Both expression levels and the subcellular localization could participate determining the functional roles of connexins in cancer. Compounds targeting connexins were thus tested as potential therapeutics intervening metastasis or chemoresistance. This review focuses on the recent findings in the correlation between the expression of connexins and patients’ prognosis, their roles in metastasis and chemoresistance, as well as the implications and concerns of using connexin-targeting drugs as anti-metastatic therapeutics. Overall, connexins may serve as biomarkers for cancer prognosis and as therapeutic targets for intervening metastasis and chemoresistance.

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“…25 In another study in the same direction, Bertram 26 reported that increasing Cx43 expression reduced normal and neoplastic tissue proliferation, decreased dysplastic tissue, and reduced tumor progression. In a study by Puzzo et al, 27 they reported that the expression of connexin Cx43 in poorly differentiated carcinoma was negative or poorly stained. In the study performed by Wilgenbus et al, 28 benign tumors, and some malign tumors were studied.…”

Section: Discussionmentioning

confidence: 97%

Expression of Connexin 32 and Connexin 43 in Adenomatous Polyps and Hyperplastic Polyps

Erdem

Aslan

Çankaya

et al. 2021

Online Türk Sağlık Bilimleri Dergisi

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ÖZAmaç: Konneksinler in tümör baskılayıcı bir gen yoluyla normal işleyen geçit bağlantıları sağladığı düşünülse de yeni çalışmalar çeşitli karsinom ve sarkomlarda konneksinlerin anormal artışına işaret etmektedir. Bu nedenle adenomatöz ve hiperplastik poliplerde connexin 43 (Cx43) ve connexin 32 (Cx32) ekspresyonunun araştırılması amaçlandı. Materyal ve Metot: Bu r etr ospektif çalışmaya 2014-2015 yılları arasında adenomatöz polipli 32 olgu ve hiperplastik polipli 42 olgu dahil edildi. Örnekler Cx43 ve Cx32 ile immünohistokimyasal boyama yöntemi ile boyandı ve değerlendirildi. Bulgular: Çalışmamızda, hiper plastik polipler de adenomatöz poliplere göre Cx43 ve Cx32 boyanmalarının arttığını gözlemledik (sırasıyla p=0,039, p=0,048). İstatistiksel olarak yaş, cinsiyet, yerleşim yeri ve çap ile boyama paterni arasında anlamlı bir ilişki yoktu. Sonuç: Adenomatöz polipler de Cx43 ve Cx32 boyanmasının azaldığı ve bu durumun displazi ile ilişkili olduğu düşünüldü.

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Connexin 43 (Cx43) Expression in Laryngeal Squamous Cell Carcinomas: Preliminary Data on Its Possible Prognostic Role

Cited by 17 publications

References 21 publications

The Potential Impact of Connexin 43 Expression on Bcl-2 Protein Level and Taxane Sensitivity in Head and Neck Cancers–In Vitro Studies

The Potential Impact of Connexin 43 Expression on Bcl-2 Protein Level and Taxane Sensitivity in Head and Neck Cancers–In Vitro Studies

Emerging roles of gap junction proteins connexins in cancer metastasis, chemoresistance and clinical application

Expression of Connexin 32 and Connexin 43 in Adenomatous Polyps and Hyperplastic Polyps

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