ArticleThe Journal of clinical investigation2023
EMT-activated secretory and endocytic vesicular trafficking programs underlie a vulnerability to PI4K2A antagonism in lung cancer.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 19 citations in OpenAlex.
- EMT activates ER-to-Golgi trafficking through upregulation of REEP2 to promote lung cancer progression.Research square · 2026Article
- Comparative Transcriptomic Profiling Reveals Differences in Initiation of Antiviral Response in Low rAAV Producing HEK293 Suspension Cells.Biotechnology journal · 2026Article
- FBXW7α regulates amyloid pathology by mediating ubiquitination and degradation of BACE1 in Alzheimer's disease.Cell death discovery · 2026Article
- Osimertinib activates a TGF-β2-dependent secretory program that drives lung adenocarcinoma progression.The Journal of clinical investigation · 2026Article
- EMT activates ER-to-Golgi trafficking through upregulation of REEP2 to promote lung cancer progression.bioRxiv : the preprint server for biology · 2025Article
- Monensin suppresses EMT-driven cancer cell motility by inducing Golgi pH-dependent exocytosis of GOLIM4.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Dichotomous roles of ACBD3 in NSCLC growth and metastasis.Oncogene · 2025Article
- SOX3 facilitates granulosa cell proliferation and suppresses cell apoptosis through modulating PI3K/AKT pathway by targeting SPP1.Cellular and molecular life sciences : CMLS · 2025Article
- Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities.Nature reviews. Cancer · 2025Review
- Phosphatidylinositol 4-phosphate; A minor lipid with multiple personalities.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2025Review
- Periostin-mediated NOTCH1 activation between tumor cells and HSCs crosstalk promotes liver metastasis of small cell lung cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Identification of the GABARAP binding determinant in PI4K2A.Bioscience reports · 2024Article
- The cancer-associated secretory phenotype: a new frontier in targeted therapeutics.The Journal of clinical investigation · 2024Review
- Targeting the secretory program of 3q-amplified lung cancers.The Journal of clinical investigation · 2024Article
- Article
- An advanced comprehensive muti-cell-type-specific model for predicting anti-PD-1 therapeutic effect in melanoma.Theranostics · 2024Article
- Analysis of the mRNA export protein ZC3H11A in HCMV infection and pan-cancer.Frontiers in microbiology · 2023Article
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10 authors at 2 institutions in 2 countries.
Funding
Abstract
Hypersecretory malignant cells underlie therapeutic resistance, metastasis, and poor clinical outcomes. However, the molecular basis for malignant hypersecretion remains obscure. Here, we showed that epithelial-mesenchymal transition (EMT) initiates exocytic and endocytic vesicular trafficking programs in lung cancer. The EMT-activating transcription factor zinc finger E-box-binding homeobox 1 (ZEB1) executed a PI4KIIIβ-to-PI4KIIα (PI4K2A) dependency switch that drove PI4P synthesis in the Golgi and endosomes. EMT enhanced the vulnerability of lung cancer cells to PI4K2A small-molecule antagonists. PI4K2A formed a MYOIIA-containing protein complex that facilitated secretory vesicle biogenesis in the Golgi, thereby establishing a hypersecretory state involving osteopontin (SPP1) and other prometastatic ligands. In the endosomal compartment, PI4K2A accelerated recycling of SPP1 receptors to complete an SPP1-dependent autocrine loop and interacted with HSP90 to prevent lysosomal degradation of AXL receptor tyrosine kinase, a driver of cell migration. These results show that EMT coordinates exocytic and endocytic vesicular trafficking to establish a therapeutically actionable hypersecretory state that drives lung cancer progression.
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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.