ArticleOncotarget2015
NHE9 induces chemoradiotherapy resistance in esophageal squamous cell carcinoma by upregulating the Src/Akt/β-catenin pathway and Bcl-2 expression.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Endosomal system genetics and autism spectrum disorders: A literature review.Neuroscience and biobehavioral reviews · 2016Pooled it
- An Endosomal Acid-Regulatory Feedback System Rewires Cytosolic cAMP Metabolism and Drives Tumor Progression.Molecular cancer research : MCR · 2024Article
- Article
- Prediction of recurrence free survival for esophageal cancer patients using a protein signature based risk model.Oncotarget · 2022Article
- Emerging links between endosomal pH and cancer.Cancer metastasis reviews · 2020Review
- Review
- Overexpression of microRNA-1470 promotes proliferation and migration, and inhibits senescence of esophageal squamous carcinoma cells.Oncology letters · 2017Article
- Comparison of right- and left-approach esophagectomy for elderly patients with operable thoracic esophageal squamous cell carcinoma: a propensity matched study.Journal of thoracic disease · 2017Article
- Hypoxia-induced mobilization of NHE6 to the plasma membrane triggers endosome hyperacidification and chemoresistance.Nature communications · 2017Article
- SIX1 overexpression predicts poor prognosis and induces radioresistance through AKT signaling in esophageal squamous cell carcinoma.OncoTargets and therapy · 2017Article
- Research Advances on Pathways of Nickel-Induced Apoptosis.International journal of molecular sciences · 2015Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recently, we found that NHE9 mRNA was upregulated in chemoradiotherapy (CRT)-resistant esophageal squamous cell carcinoma (ESCC); however, the underlying mechanisms were unclear. Here, we aimed to clarify the functional contribution of NHE9 to CRT resistance, understand the molecular basis of NHE9-dependent resistance in ESCC, and identify potential therapeutic targets. Our results showed that NHE9 prevented CRT-induced apoptosis. Importantly, we found that RACK1 is a novel binding partner of NHE9 and that NHE9-dependent induction of CRT resistance requires the activation of RACK1-associated Src/Akt/β-catenin signaling. Moreover, upregulated Bcl-2 protein was also observed in cells exhibiting NHE9-induced CRT resistance. A higher NHE9 level was associated with a poor response to CRT and less decrease in T and N stage in ESCC patients. Furthermore, combining either Dasatinib or ABT-737 with CRT significantly reduced tumor volume, and the response to CRT was restored when these inhibitors were used together with CRT in a xenograft nude mouse model with NHE9 overexpression. Taken together, our findings demonstrate that NHE9 can be an effective predictor of CRT response and may be useful in the development of targeted therapies for CRT-resistant ESCC.
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