ArticleLaboratory investigation; a journal of technical methods and pathology2018
ARHGEF39 promotes tumor progression via activation of Rac1/P38 MAPK/ATF2 signaling and predicts poor prognosis in non-small cell lung cancer patients.
Article in Laboratory investigation; a journal of technical methods and pathology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 26 citations in OpenAlex.
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- Identification of key genes to predict response to chemoradiotherapy and prognosis in esophageal squamous cell carcinoma.Frontiers in molecular biosciences · 2024Article
- DeepCBS: shedding light on the impact of mutations occurring at CTCF binding sites.Frontiers in genetics · 2024Article
- The E3 ubiquitin ligase MG53 inhibits hepatocellular carcinoma by targeting RAC1 signaling.Oncogenesis · 2022Article
- Tonifying-Qi-and-Detoxification Decoction attenuated injuries of colon and lung tissues in ulcerative colitis rat model via regulating NF-κB and p38MAPK pathway.Annals of translational medicine · 2022Article
- Identification of cuproptosis-related gene signature to predict prognosis in lung adenocarcinoma.Frontiers in genetics · 2022Article
- Article
- FARP1, ARHGEF39, and TIAM2 are essential receptor tyrosine kinase effectors for Rac1-dependent cell motility in human lung adenocarcinoma.Cell reports · 2021Article
- Novel insights into the RTK-dependent metastatic phenotype of KRAS-mutant lung adenocarcinoma.Molecular & cellular oncology · 2021Article
- Novel prognostic molecular markers in lung cancer.Oncology letters · 2020Review
- MicroRNA Regulation of the Small Rho GTPase Regulators-Complexities and Opportunities in Targeting Cancer Metastasis.Cancers · 2020Review
- Rho guanine nucleotide exchange factor 39 increases the viability, migration and invasion of clear cell renal cell carcinoma cells via the activation of the AKT/ERK signaling pathway.Genetics and molecular biology · 2020Article
- Review
- Expression of Rho Guanine Nucleotide Exchange Factor 39 (ARHGEF39) and Its Prognostic Significance in Hepatocellular Carcinoma.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- FAM163A, a positive regulator of ERK signaling pathway, interacts with 14-3-3β and promotes cell proliferation in squamous cell lung carcinoma.OncoTargets and therapy · 2019Article
- Comprehensive investigation of alternative splicing and development of a prognostic risk score for prostate cancer based on six-gene signatures.Journal of Cancer · 2019Article
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8 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Rho guanine nucleotide exchange factor 39 (ARHGEF39), also called C9orf100, is a new member of the Dbl-family of guanine nucleotide exchange factors. Although ARHGEF39 has been proven to regulate tumor progression in hepatocellular carcinoma, the downstream signaling pathway of ARHGEF39 and its clinical associations in non-small cell lung cancer (NSCLC) are currently unknown. In the present study, using MTT, colony formation, flow cytometry, mice xenografts, wound healing, and transwell assays, we showed that ARHGEF39 promoted tumor proliferation, migration, and invasion. Furthermore, ARHGEF39 promoted the expression of Cyclin A2, Cyclin D1, and MMP2 by activating Rac1, leading to increased phosphorylation of P38 and ATF2. Treatment with a P38 inhibitor counteracted the effect of ARHGEF39 overexpression on the increase in Cyclin A2, Cyclin D1, and MMP2 expression. Moreover, the elevated levels of p-P38 and p-ATF2 caused by ARHGEF39 overexpression could be inhibited by expression of a dominant negative Rac1 mutant (T17N). In addition, the inhibition of the expression of p-P38 and p-ATF2 by ARHGEF39 RNAi could be restored by the expression of a constitutively active Rac1 mutant (Q61L). A similar impact on cell growth and invasion was observed after ARHGEF39 overexpression combined with the P38 inhibitor, Rac1 T17N, or Rac1 Q61L. Using immunohistochemistry, ARHGEF39 expression was observed to correlate positively with larger tumor size in clinical samples from 109 cases of NSCLC (P = 0.008). The Kaplan-Meier test revealed that ARHGEF39 expression significantly affected the overall survival of patients with NSCLC (52.55 ± 6.40 months vs. 64.30 ± 5.40 months, P = 0.017). In conclusion, we identified that ARHGEF39 promotes tumor growth and invasion by activating the Rac1-P38-ATF2 signaling pathway, as well as increasing the expression of Cyclin A2, Cyclin D1, and MMP2 in NSCLC cells. ARHGEF39 may be a useful marker to predict poor prognosis of patients with NSCLC.
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