ArticleCell reports. Medicine2023
HOXC6 drives a therapeutically targetable pancreatic cancer growth and metastasis pathway by regulating MSK1 and PPP2R2B.
Article in Cell reports. Medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 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
- A multiomics Mendelian randomization study on PANoptosis-related genes and gastric cancer risk.The Journal of international medical research · 2026Article
- HOXC6 overexpression stimulates cell migration and correlates with poor prognosis in head and neck squamous cell carcinoma.Cellular and molecular life sciences : CMLS · 2026Article
- Multiomics Identification of Radioresistance-Associated Biomarkers and Prognostic Model Construction in Rectal Cancer.Human mutation · 2026Article
- Integrated single-cell and bulk transcriptomics identify autophagy-related immune-suppressive subtypes and a prognostic signature in colorectal cancer.Frontiers in immunology · 2026Article
- CRX is an intrinsic suppressor of epithelial‒mesenchymal transition in retinal pigment epithelial cells: a promising therapeutic avenue for subretinal fibrosis.Cell death & disease · 2025Article
- A novel defined manganese metabolism-related gene signature for predicting the prognosis of pancreatic ductal adenocarcinoma.Oncology letters · 2025Article
- HOXC6-TIMELESS axis: Unveiling novel therapeutic strategies in bladder cancer.World journal of clinical oncology · 2025Article
- Homeobox C6 plays an oncogenic role in bladder cancer.World journal of clinical oncology · 2025Article
- Transcriptome associated with single-cell analysis reveal the role of S-palmitoylation in coronary artery disease.Scientific reports · 2025Article
- HDAC and MEK inhibition synergistically suppresses HOXC6 and enhances PD-1 blockade efficacy in BRAFJournal for immunotherapy of cancer · 2025Article
- The advances of DEAD-box RNA helicase 17 in chronic non-infectious diseases.Frontiers in cardiovascular medicine · 2025Review
- Cross-cohort multi-omics analysis identifies novel clusters driven by EMT signatures in colorectal cancer.Frontiers in immunology · 2025Article
- Exploring the prognosis value, immune correlation, and drug responsiveness prediction of homeobox C6 (HOXC6) in lung adenocarcinoma.Discover oncology · 2024Article
- Comprehensive analysis of mitochondria-related genes indicates that PPP2R2B is a novel biomarker and promotes the progression of bladder cancer via Wnt signaling pathway.Biology direct · 2024Article
- Everolimus in pituitary tumor: a review of preclinical and clinical evidence.Frontiers in endocrinology · 2024Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, which lacks effective therapies. Here, we demonstrate that the transcription factor, homeobox C6 (HOXC6), is overexpressed in most PDACs, and its inhibition blocks PDAC tumor growth and metastasis. HOXC6 transcriptionally activates tumor-promoting kinase MSK1 and suppresses tumor-inhibitory protein PPP2R2B in PDAC. HOXC6-induced PPP2R2B suppression causes mammalian target of rapamycin (mTOR) pathway activation, which facilitates PDAC growth. Also, MSK1 upregulation by HOXC6 is necessary for PDAC growth because of its ability to suppress apoptosis via its substrate DDX17. Combinatorial pharmacological inhibition of MSK1 and mTOR potently suppressed PDAC tumor growth and metastasis in PDAC mouse models. PDAC cells with acquired resistance to MSK1/mTOR-inhibitors displayed activated insulin-like growth factor 1 receptor (IGF1R) signaling and were successfully eradicated by IGF1R inhibitor. Furthermore, MEK inhibitor trametinib enhanced the efficacy of dual MSK1 and mTOR inhibition. Collectively, these results identify therapeutic vulnerabilities of PDAC and an approach to overcome acquired drug resistance to prolong therapeutic benefit.
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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.