ArticleJCI insight2018
Semaphorin 7A promotes EGFR-TKI resistance in EGFR mutant lung adenocarcinoma cells.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Pathogenic mechanisms and resistance profiles of microbial pulmonary infections in lung cancer: a systematic review.BMC infectious diseases · 2025Pooled it
- A Phase II Study of Modified FOLFOX6 for Advanced Gastric Cancer Refractory to Standard Therapies.Advances in therapy · 2020Trial
- Targeting Semaphorin 7a signaling in preclinical models of endocrine therapy-resistant breast cancer.Molecular cancer therapeutics · 2026Article
- Sema7a drives an immunosuppressive microenvironment of breast cancer via Kdm4a-mediated DNA replication regulation.Communications biology · 2025Article
- The changes of immune function after neuroblastoma chemotherapy and the prediction of potential immune targets.BMC medical genomics · 2025Article
- SKA3 promotes lung adenocarcinoma progression via the EGFR/E2F1/SKA3/integrin β1 signaling loop.Molecular and cellular biochemistry · 2025Article
- Article
- Protein phosphorylation regulation of key genes in oral squamous cell carcinoma and their role in the immune microenvironment.Frontiers in immunology · 2025Article
- Associations of SEMA7A, SEMA4D, ADAMTS10, and ADAM8 with KRAS, NRAS, BRAF, PIK3CA, and AKT Gene Mutations, Microsatellite Instability Status, and Cytokine Expression in Colorectal Cancer Tissue.Current issues in molecular biology · 2024Article
- FUT8-mediated aberrant N-glycosylation of SEMA7A promotes head and neck squamous cell carcinoma progression.International journal of oral science · 2024Article
- Sema6D forward signaling impairs T cell activation and proliferation in head and neck cancer.JCI insight · 2024Article
- A comprehensive review on lncRNA LOXL1-AS1: molecular mechanistic pathways of lncRNA LOXL1-AS1 in tumorigenicity of cancer cells.Frontiers in oncology · 2024Review
- Pan-Cancer Analysis of the Prognostic and Immunological Role of SEMA7A.International journal of general medicine · 2024Article
- SEMA7A as a Novel Prognostic Biomarker and Its Correlation with Immune Infiltrates in Breast Cancer.International journal of general medicine · 2024Article
- Analyzing aberrant DNA methylation in colorectal cancer uncovered intangible heterogeneity of gene effects in the survival time of patients.Scientific reports · 2023Article
- Semaphorins and Their Roles in Breast Cancer: Implications for Therapy Resistance.International journal of molecular sciences · 2023Review
- USP51/PD-L1/ITGB1-deployed juxtacrine interaction plays a cell-intrinsic role in promoting chemoresistant phenotypes in non-small cell lung cancer.Cancer communications (London, England) · 2023Article
- Analyzing aberrant DNA methylation in Colorectal cancer uncovered intangible heterogeneity of gene effects in the survival time of patients.Research square · 2023Article
- Breast cancers co-opt normal mechanisms of tolerance to promote immune evasion and metastasis.American journal of physiology. Cell physiology · 2022Review
- Betacellulin promotes tumor development and EGFR mutant lung cancer growth by stimulating the EGFR pathway and suppressing apoptosis.iScience · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
35 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although responses to EGFR tyrosine kinase inhibitors (EGFR-TKIs) are initially positive, 30%-40% of patients with EGFR-mutant tumors do not respond well to EGFR-TKIs, and most lung cancer patients harboring EGFR mutations experience relapse with resistance. Therefore, it is necessary to identify not only the mechanisms underlying EGFR-TKI resistance, but also potentially novel therapeutic targets and/or predictive biomarkers for EGFR-mutant lung adenocarcinoma. We found that the GPI-anchored protein semaphorin 7A (SEMA7A) is highly induced by the EGFR pathway, via mTOR signaling, and that expression levels of SEMA7A in human lung adenocarcinoma specimens were correlated with mTOR activation. Investigations using cell culture and animal models demonstrated that loss or overexpression of SEMA7A made cells less or more resistant to EGFR-TKIs, respectively. The resistance was due to the inhibition of apoptosis by aberrant activation of ERK. The ERK signal was suppressed by knockdown of integrin β1 (ITGB1). Furthermore, in patients with EGFR mutant tumors, higher SEMA7A expression in clinical samples predicted poorer response to EGFR-TKI treatment. Collectively, these data show that the SEMA7A-ITGB1 axis plays pivotal roles in EGFR-TKI resistance mediated by ERK activation and apoptosis inhibition. Moreover, our results reveal the potential utility of SEMA7A not only as a predictive biomarker, but also as a potentially novel therapeutic target in EGFR-mutant lung adenocarcinoma.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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 OpenQuestion graph.