ArticleInternational immunopharmacology2015
Role of Lynx1 and related Ly6 proteins as modulators of cholinergic signaling in normal and neoplastic bronchial epithelium.
Article in International immunopharmacology, 2015. 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, 32 citations in OpenAlex.
- A Noninvasive Circulating Tumor DNA Methylation Classifier to Identify Benign Pulmonary Nodules.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Unveiling the Importance of the Expression of LY6/UPAR Gene Family Members in Urothelial Carcinoma of the Urinary Bladder.Biomedicines · 2026Article
- Ly6/uPAR Protein fromMarine drugs · 2025Article
- Targeting Alpha7 Nicotinic Acetylcholine Receptors in Lung Cancer: Insights, Challenges, and Therapeutic Strategies.ACS pharmacology & translational science · 2024Review
- Exploring tumor-normal cross-talk with TranNet: Role of the environment in tumor progression.PLoS computational biology · 2023Article
- Exploring tumor-normal cross-talk with TranNet: role of the environment in tumor progression.bioRxiv : the preprint server for biology · 2023Article
- Ambient air pollution during pregnancy and DNA methylation in umbilical cord blood, with potential mediation of associations with infant adiposity: The Healthy Start study.Environmental research · 2022Article
- Nicotinic Acetylcholine Receptors in the Respiratory Tract.Molecules (Basel, Switzerland) · 2021Review
- α9-Containing Nicotinic Receptors in Cancer.Frontiers in cellular neuroscience · 2021Review
- SLURP-1 Controls Growth and Migration of Lung Adenocarcinoma Cells, Forming a Complex With α7-nAChR and PDGFR/EGFR Heterodimer.Frontiers in cell and developmental biology · 2021Article
- Mediation by differential DNA methylation of known associations between single nucleotide polymorphisms and bladder cancer risk.BMC medical genetics · 2020Article
- Structural Diversity and Dynamics of Human Three-Finger Proteins Acting on Nicotinic Acetylcholine Receptors.International journal of molecular sciences · 2020Article
- Increased Expression of LYNX1 in Ovarian Serous Cystadenocarcinoma Predicts Poor Prognosis.BioMed research international · 2020Article
- Acetylcholine signaling system in progression of lung cancers.Pharmacology & therapeutics · 2019Review
- Article
- Emerging Role of Lymphocyte Antigen-6 Family of Genes in Cancer and Immune Cells.Frontiers in immunology · 2019Review
- Attached stratified mucus separates bacteria from the epithelial cells in COPD lungs.JCI insight · 2018Article
- Proteins and chemical chaperones involved in neuronal nicotinic receptor expression and function: an update.British journal of pharmacology · 2018Review
- Human secreted proteins SLURP-1 and SLURP-2 control the growth of epithelial cancer cells via interactions with nicotinic acetylcholine receptors.British journal of pharmacology · 2018Article
- Neuronal and Extraneuronal Nicotinic Acetylcholine Receptors.Current neuropharmacology · 2018Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The ly-6 proteins are a large family of proteins that resemble the snake three finger alpha toxins such as α-bungarotoxin and are defined by their multiple cysteine residues. Multiple members of the ly-6 protein family can modulate nicotinic signaling including lynx1, lynx2, slurp-1, slurp-2 and prostate stem cell antigen (PSCA). Consistent with the expression of multiple nicotinic receptors in bronchial epithelium, multiple members of the nicotinic-modulatory ly-6 proteins are expressed in lung including lynx1 and lynx2. We studied the role of lynx1 as an exemplar of the role of ly-6 proteins in lung. Our data demonstrates that lynx1 acts as a negative modulator of nicotinic signaling in normal and neoplastic lung. In normal lung lynx1 serves to limit the ability of chronic nicotine exposure to increase levels of nicotinic receptors and also serves to limit the ability of nicotine to upregulate levels of GABAA receptors in lung. In turn this allows lynx1 to limit the ability of nicotine to upregulate levels of mucin which is mediated by GABAergic signaling. This suggests that lynx1-mimetics may have potential for treatment of asthma and COPD. In that most lung cancer cells also express nicotinic receptor and lynx1 we examined the role of lynx-1 in lung cancer. Lynx1 levels are decreased in lung cancers compared to adjacent normal lung. Knockdown of lynx1 by siRNAs increased growth of lung cancer cells while expression of lynx1 in lung cancer cell decreased cell proliferation. This suggests that lynx1 is an endogenous regulator of lung cancer growth. Given that multiple small molecule negative and positive allosteric modulators of nicotinic receptors have already been developed, this suggests that lynx1 is a highly druggable target both for development of drugs that may limit lung cancer growth as well as for drugs that may be effective for asthma or COPD treatment.
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