ArticleOncogene2012
PAK1 is a breast cancer oncogene that coordinately activates MAPK and MET signaling.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 1 of them a synthesis that pooled it.
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Who cites it
104 citing papers in PubMed, 1 synthesis or guideline pooled it, 165 citations in OpenAlex.
- Systematic review and meta-analysis of genomic alterations in acral melanoma.Pigment cell & melanoma research · 2022Pooled it
- Development of NanoBRET cellular target engagement assays in primary neurons for activating mutants of p21-activated kinase 1.bioRxiv : the preprint server for biology · 2026Article
- Berry-derived gold nanoparticles induce integrated ROS-mediated apoptosis, immune modulation, and transcriptomic remodeling in 4T1 triple-negative cancer cells.Cell death discovery · 2026Article
- Proteomics and phosphoproteomics of human colorectal cancer cells lacking a specific kinase activity reveal kinase-specific compensatory responses.Animal cells and systems · 2026Article
- Exosomal transfer of miR-223-3p from carcinoma-associated fibroblasts promotes the malignant properties and chemoresistance of colon cancer cells by targeting NF2/Hippo signaling.Medical oncology (Northwood, London, England) · 2025Article
- PAK1 regulates oligodendroglial proliferation and repopulation in homeostatic and demyelinating brain.Cellular and molecular life sciences : CMLS · 2025Article
- Identifying and Targeting Key Driver Genes for Collagen Production within the 11q13/14 Breast Cancer Amplicon.Molecular cancer research : MCR · 2025Article
- The Role of the p21-Activated Kinase Family in Tumor Immunity.International journal of molecular sciences · 2025Review
- Integrated spatial multi-omics profiling of Fusobacterium nucleatum in breast cancer unveils its role in tumour microenvironment modulation and cancer progression.Clinical and translational medicine · 2025Article
- The expression of congenital Shoc2 variants induces AKT-dependent crosstalk activation of the ERK1/2 pathway.Human molecular genetics · 2024Article
- Control of OPC proliferation and repopulation by the intellectual disability gene PAK1 under homeostatic and demyelinating conditions.bioRxiv : the preprint server for biology · 2024Article
- KinPred-RNA-kinase activity inference and cancer type classification using machine learning on RNA-seq data.iScience · 2024Article
- Translational profiling reveals novel gene expression changes in the direct and indirect pathways in a mouse model of levodopa induced dyskinesia.Frontiers in cellular neuroscience · 2024Article
- Prolactin-induced tyrosyl phosphorylation of PAK1 facilitates epithelial-mesenchymal transition.microPublication biology · 2024Article
- Generating a Murine PTEN Null Cell Line to Discover the Key Role of p110β-PAK1 in Castration-Resistant Prostate Cancer Invasion.Molecular cancer research : MCR · 2023Article
- Pak1 pathway hyper-activation mediates resistance to endocrine therapy and CDK4/6 inhibitors in ER+ breast cancer.NPJ breast cancer · 2023Article
- The direct effect of fibroblast growth factor 23 on vascular smooth muscle cell phenotype and function.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2023Article
- Adolescent- and adult-initiated alcohol exposure in mice differentially promotes tumorigenesis and metastasis of breast cancer.Alcohol, clinical & experimental research · 2023Article
- Catechol-O-methyl transferase suppresses cell invasion and interplays with MET signaling in estrogen dependent breast cancer.Scientific reports · 2023Article
- PAK1 copy number in breast cancer-Associations with proliferation and molecular subtypes.PloS one · 2023Article
44 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
Activating mutations in the RAS family or BRAF frequently occur in many types of human cancers but are rarely detected in breast tumors. However, activation of the RAS-RAF-MEK-ERK MAPK pathway is commonly observed in human breast cancers, suggesting that other genetic alterations lead to activation of this signaling pathway. To identify breast cancer oncogenes that activate the MAPK pathway, we screened a library of human kinases for their ability to induce anchorage-independent growth in a derivative of immortalized human mammary epithelial cells (HMLE). We identified p21-activated kinase 1 (PAK1) as a kinase that permitted HMLE cells to form anchorage-independent colonies. PAK1 is amplified in several human cancer types, including 30--33% of breast tumor samples and cancer cell lines. The kinase activity of PAK1 is necessary for PAK1-induced transformation. Moreover, we show that PAK1 simultaneously activates MAPK and MET signaling; the latter via inhibition of merlin. Disruption of these activities inhibits PAK1-driven anchorage-independent growth. These observations establish PAK1 amplification as an alternative mechanism for MAPK activation in human breast cancer and credential PAK1 as a breast cancer oncogene that coordinately regulates multiple signaling pathways, the cooperation of which leads to malignant transformation.
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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.