ArticleClinical and translational medicine2022
A novel EHD1/CD44/Hippo/SP1 positive feedback loop potentiates stemness and metastasis in lung adenocarcinoma.
Article in Clinical and translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 33 citations in OpenAlex.
- A Quarter Century of EHD Protein Research: From Endosomal Recycling to Ciliopathies.Traffic (Copenhagen, Denmark) · 2026Review
- SP1 lactylation promotes endometrial cancer cell stemness via regulation of CENPL expression.Genes & diseases · 2026Article
- Loop of N2-polarized neutrophils and exhausted CD8 + T cells induces immunotherapy resistance in NSCLC.Molecular and cellular biochemistry · 2026Article
- PTTG1-DLX2 axis drives malignant progression of lung adenocarcinoma by activating the WNT/β-catenin signaling pathway.Translational cancer research · 2026Article
- From Environmental Risk to Cancer Stemness: Epigenetic Regulation in Oral Squamous Cell Carcinoma.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Imaging-based development and validation of artificial intelligence models for lung adenocarcinoma precursor lesions and early lung adenocarcinoma presenting as pulmonary nodules.Frontiers in artificial intelligence · 2026Article
- Cuproptosis in lung cancer: a nexus of ncRNA regulation, epigenetics, and tumor microenvironment Remodeling.Clinical and experimental medicine · 2025Review
- MS4A1 regulates M1-polarized tumor-associated macrophage infiltration, angiogenesis, and cancer progression through the HIPPO pathway in lung adenocarcinoma.Cancer immunology, immunotherapy : CII · 2025Article
- mCancer communications (London, England) · 2025Article
- Regulating chemoresistance and cancer stemness: the CDH17-YAP pathway in distinct cellular states of lung cancer CTC clusters.Cellular & molecular biology letters · 2025Article
- The MIR181A2HG/miR-5680/VCAN-CD44 Axis Regulates Gastric Cancer Lymph Node Metastasis by Promoting M2 Macrophage Polarization.Cancer medicine · 2025Article
- SP1 undergoes phase separation and activates RGS20 expression through super-enhancers to promote lung adenocarcinoma progression.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Compartmentalization proteomics revealed endolysosomal protein network changes in a goat model of atrial fibrillation.iScience · 2024Article
- CD44 and its implication in neoplastic diseases.MedComm · 2024Review
- Hippo pathway in non-small cell lung cancer: mechanisms, potential targets, and biomarkers.Cancer gene therapy · 2024Review
- Systematic Analysis to Identify the MIR99AHG-has-miR-21-5p-Journal of Cancer · 2024Article
- YY1 modulates the radiosensitivity of esophageal squamous cell carcinoma through KIF3B-mediated Hippo signaling pathway.Cell death & disease · 2023Article
- CD44 Intracellular Domain: A Long Tale of a Short Tail.Cancers · 2023Review
- Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThere is growing evidence that endocytosis plays a pivotal role in cancer metastasis. In this study, we first identified endocytic and metastasis-associated genes (EMGs) and then investigated the biological functions and mechanisms of EMGs.
methodsCancer stem cells (CSCs)-like characteristics were evaluated by tumour limiting dilution assays, three-dimensional (3D) spheroid cancer models. Microarray analysis was used to identify the pathways significantly regulated by mammalian Eps15 homology domain protein 1 (EHD1) knockdown. Mass spectrometry (MS) was performed to identify EHD1-interacting proteins. The function of EHD1 as a regulator of cluster of differentiation 44 (CD44) endocytic recycling and lysosomal degradation was determined by CD44 biotinylation and recycling assays.
resultsEHD1 was identified as a significant EMG. Knockdown of EHD1 suppressed CSCs-like characteristics, epithelial-mesenchymal transition (EMT), migration and invasion of lung adenocarcinoma (LUAD) cells by increasing Hippo kinase cascade activation. Conversely, EHD1 overexpression inhibited the Hippo pathway to promote cancer stemness and metastasis. Notably, utilising MS analysis, the CD44 protein was identified as a potential binding partner of EHD1. Furthermore, EHD1 enhanced CD44 recycling and stability. Indeed, silencing of CD44 or disruption of the EHD1/CD44 interaction enhanced Hippo pathway activity and reduced CSCs-like traits, EMT and metastasis. Interestingly, specificity protein 1 (SP1), a known downstream target gene of the Hippo-TEA-domain family members 1 (TEAD1) pathway, was found to directly bind to the EHD1 promoter region and induce its expression. Among clinical specimens, the EHD1 expression level in LUAD tissues of metastatic patients was higher than that of non-metastatic patients.
conclusionsOur findings emphasise that EHD1 might be a potent anti-metastatic target and present a novel regulatory mechanism by which the EHD1/CD44/Hippo/SP1 positive feedback circuit plays pivotal roles in coupling modules of CSCs-like properties and EMT in LUAD. Targeting this loop may serve as a remedy for patients with advanced metastatic LUAD.
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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.