ArticleOncogene2019
Gjb4 serves as a novel biomarker for lung cancer and promotes metastasis and chemoresistance via Src activation.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- Cx58 is associated with the metastasis of non-small cell lung cancer via MEF2B/Cx58 axis.Acta biochimica et biophysica Sinica · 2025Article
- Clinical and pathological implications of the presence of MECA-79-expressing tumor cells in pathological stage IA lung adenocarcinoma.PloS one · 2025Article
- Targeting GJB4 to inhibit tumor growth and induce ferroptosis in pancreatic cancer.Frontiers in oncology · 2025Article
- Gap junction beta-4 accelerates cell cycle progression and metastasis through MET-AKT activation in pancreatic cancer.Cancer science · 2024Article
- Interplay between paclitaxel, gap junctions, and kinases: unraveling mechanisms of action and resistance in cancer therapy.Molecular biology reports · 2024Review
- Cell Death, by Any Other Name….Cells · 2024Review
- Multi-omics analysis of expression profile and prognostic values of connexin family in LUAD.Journal of cancer research and clinical oncology · 2023Article
- The Multifaceted Role of Connexins in Tumor Microenvironment Initiation and Maintenance.Biology · 2023Review
- Establishment of a 7-gene prognostic signature based on oxidative stress genes for predicting chemotherapy resistance in pancreatic cancer.Frontiers in pharmacology · 2023Article
- Drug repositioning in non-small cell lung cancer (NSCLC) using gene co-expression and drug-gene interaction networks analysis.Scientific reports · 2022Article
- Wogonin increases gemcitabine sensitivity in pancreatic cancer by inhibiting Akt pathway.Frontiers in pharmacology · 2022Article
- Identification of a 3-Gene Prognostic Index for Papillary Thyroid Carcinoma.Frontiers in molecular biosciences · 2022Article
- The prognostic value and biological significance of gap junction beta protein 2 (GJB2 or Cx26) in cervical cancer.Frontiers in oncology · 2022Article
- Connexin32 activates necroptosis through Src-mediated inhibition of caspase 8 in hepatocellular carcinoma.Cancer science · 2021Article
- Connexins-Therapeutic Targets in Cancers.International journal of molecular sciences · 2020Review
- Dasatinib reverses drug resistance by downregulating MDR1 and Survivin in Burkitt lymphoma cells.BMC complementary medicine and therapies · 2020Article
- Connexins in Lung Cancer and Brain Metastasis.Frontiers in oncology · 2020Review
- Connexins in cancer: bridging the gap to the clinic.Oncogene · 2019Review
- Article
- Emerging roles of gap junction proteins connexins in cancer metastasis, chemoresistance and clinical application.Journal of biomedical science · 2019Review
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
Most lung cancer patients are diagnosed late with metastasis, which is the major cause of cancer-related death and recurrent tumors that often exhibit chemoresistance. In the present study, we initially identified gap junction beta-4 protein (Gjb4) to be overexpressed in highly metastatic cancer cells selected by their enhanced binding to serum components. Overexpression or knockdown of Gjb4 increased or decreased lung metastasis of syngeneic mice, respectively. We found that Gjb4 expression was higher in lung tumors than normal tissues (p = 0.0026), and Gjb4 levels in blood buffy coat samples showed significant performance in diagnosing stage I-III (p = 0.002814) and stage IV (p < 0.0001) lung cancer. Moreover, high Gjb4 expression levels were correlated with poor prognosis (p = 1.4e-4) and recurrence (p = 1.9e-12). Using syngeneic mouse model, we observed that Gjb4 was able to promote tumor growth. High molecular weight serum fraction containing the major growth factor component IGF1 was able to induce Gjb4 via PKC pathway. Gjb4 activated Src signaling via MET, and overexpression of Gjb4 enhanced sphere-forming ability and anchorage-independent growth, which were reversed by inhibition of Src. In addition, we demonstrated that Gjb4-mediated Src activation enhanced chemoresistance of cancer cells toward gemcitabine and etoposide. The combination of Gjb4 knockdown, gemcitabine, and dasatinib further enhanced the inhibition of cancer cell viability. Together, our study has identified Gjb4 as a potential novel diagnostic and prognostic biomarker for lung cancer. Targeting Gjb4 may be exploited as a modality for improving lung cancer therapy.
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