ArticleInternational journal of oncology2019
Hypoxia‑induced internalization of connexin 26 and connexin 43 in pulmonary epithelial cells is involved in the occurrence of non‑small cell lung cancer via the P53/MDM2 signaling pathway.
Article in International journal of oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 34 citations in OpenAlex.
- Gap Junction-Mediated Communication in Melanoma: From Tumor Progression to Treatment Response.International journal of molecular sciences · 2026Review
- HIF-1α-Mediated Disruption of Cellular Junctions: The Impact of Hypoxia on the Tumor Microenvironment and Invasion.International journal of molecular sciences · 2025Review
- Hypoxia studies in non‑small cell lung cancer: Pathogenesis and clinical implications (Review).Oncology reports · 2025Review
- Connexin-43 in Cancer: Above and Beyond Gap Junctions!Cancers · 2024Review
- Metformin suppresses NFE2L1 pathway activation to inhibit gap junction beta protein expression in NSCLC.Cancer medicine · 2024Article
- Intercellular Communication in Airway Epithelial Cell Regeneration: Potential Roles of Connexins and Pannexins.International journal of molecular sciences · 2023Review
- The Multifaceted Role of Connexins in Tumor Microenvironment Initiation and Maintenance.Biology · 2023Review
- Quercitrin restrains the growth and invasion of lung adenocarcinoma cells by regulating gap junction protein beta 2.Bioengineered · 2022Article
- An Analysis Regarding the Association Between Connexins and Colorectal Cancer (CRC) Tumor Microenvironment.Journal of inflammation research · 2022Article
- lncRNA LEF1-AS1 Acts as a Novel Biomarker and Promotes Hypopharyngeal Squamous Cell Carcinoma Progression and Metastasis by Targeting the miR-221-5p/GJA1 Axis.Disease markers · 2022Article
- Single-Cell RNA Sequencing Reveals the Role of Epithelial Cell Marker Genes in Predicting the Prognosis of Colorectal Cancer Patients.Disease markers · 2022Article
- A methylation-based nomogram for predicting survival in patients with lung adenocarcinoma.BMC cancer · 2021Article
- PLODs are overexpressed in ovarian cancer and are associated with gap junctions via connexin 43.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- Connexins-Therapeutic Targets in Cancers.International journal of molecular sciences · 2020Review
- High GJB2 mRNA expression and its prognostic significance in lung adenocarcinoma: a study based on the TCGA database.Medicine · 2020Observational
- Connexins in Lung Cancer and Brain Metastasis.Frontiers in oncology · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Reports have highlighted an association between connexins (CXs) or gap junction proteins and non‑small cell lung cancer (NSCLC). In the present study, it was aimed to elucidate the regulatory mechanism of CX26 and CX43 under hypoxic conditions in NSCLC. Clinical samples were collected for analysis of CX26 and CX43 expression and clinical cancerization followed by quantification of CX26 and CX43 expression. Following the establishment of an in vitro hypoxia model, P53/murine double minute‑2 (MDM2) signaling pathway‑, proliferation‑ and epithelial‑mesenchymal transition (EMT)‑related genes were quantified to evaluate the influence of CX26 and CX43 on the biological functions of pulmonary epithelial cells in NSCLC. In addition, the proliferation and tumorigenicity of cancer cells were assessed by EdU staining and xenograft tumors, respectively. Decreased expression of CX26 and CX43 was found in cancer tissues compared with surrounding normal tissue. Hypoxia was shown to activate the P53/MDM2 axis and stimulate the downregulation, ubiquitination and degradation of CX26 and CX43, which were translocated from the membrane to the cytoplasm. Low levels of CX26 and CX43 were demonstrated to further promote EMT and the induction of the proliferation and tumorigenicity of cancer cells. These results were reflected by decreased E‑cadherin expression and increased N‑cadherin expression, along with increased cell migration, promoted cell proliferation ability and elevated relative protein expression of Oct4 and Nanog, and accelerated tumor growth, accompanied by a higher number of metastatic nodes. Taken together, the key observations of the present study demonstrate that the internalization of CX26 and CX43 promoted proliferation, EMT and migration and thus induced NSCLC via aberrant activation of the P53/MDM2 signaling pathway under hypoxic conditions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.