ArticleOncogene2010
The protein kinase Pak4 disrupts mammary acinar architecture and promotes mammary tumorigenesis.
Article in Oncogene, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 70 citations in OpenAlex.
- P21-activated kinase 4: a potent oncogene, molecular mechanisms and opportunities for targeted therapy.Cancer cell international · 2025Review
- Red blood cell-tumor cell interactions promote tumor cell progression.Journal of experimental & clinical cancer research : CR · 2025Article
- Baicalein Inhibits the Growth of Transplanted Esophageal Cancer in Mice and the Effect on the Expression of PAK4.Bulletin of experimental biology and medicine · 2023Article
- Review
- The significance of PAK4 in signaling and clinicopathology: A review.Open life sciences · 2022Review
- Synthetic Heterocyclic Derivatives as Kinase Inhibitors Tested for the Treatment of Neuroblastoma.Molecules (Basel, Switzerland) · 2021Review
- Coordinated dysregulation of cancer progression by the HER family and p21-activated kinases.Cancer metastasis reviews · 2020Review
- KPT-9274, an Inhibitor of PAK4 and NAMPT, Leads to Downregulation of mTORC2 in Triple Negative Breast Cancer Cells.Chemical research in toxicology · 2020Article
- PAK4 phosphorylating RUNX1 promotes ERα-positive breast cancer-induced osteolytic bone destruction.International journal of biological sciences · 2020Article
- Nonconserved miR-608 suppresses prostate cancer progression through RAC2/PAK4/LIMK1 and BCL2L1/caspase-3 pathways by targeting the 3'-UTRs of RAC2/BCL2L1 and the coding region of PAK4.Cancer medicine · 2019Article
- PAK4 suppresses RELB to prevent senescence-like growth arrest in breast cancer.Nature communications · 2019Article
- A mandatory role of nuclear PAK4-LIFR axis in breast-to-bone metastasis of ERα-positive breast cancer cells.Oncogene · 2019Article
- Inhibition of neuroblastoma proliferation by PF-3758309, a small-molecule inhibitor that targets p21-activated kinase 4.Oncology reports · 2017Article
- Functional role and therapeutic targeting of p21-activated kinase 4 in multiple myeloma.Blood · 2017Article
- P21-activated kinase 4 involves TSH induced papillary thyroid cancer cell proliferation.Oncotarget · 2017Article
- Activated-PAK4 predicts worse prognosis in breast cancer and promotes tumorigenesis through activation of PI3K/AKT signaling.Oncotarget · 2017Article
- A novel orally bioavailable compound KPT-9274 inhibits PAK4, and blocks triple negative breast cancer tumor growth.Scientific reports · 2017Article
- Study on the expression of PAK4 and P54 protein in breast cancer.World journal of surgical oncology · 2016Article
- Minireview: Mouse Models of Rho GTPase Function in Mammary Gland Development, Tumorigenesis, and Metastasis.Molecular endocrinology (Baltimore, Md.) · 2016Review
- Group II p21-activated kinases as therapeutic targets in gastrointestinal cancer.World journal of gastroenterology · 2016Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The Pak4 serine/threonine kinase is highly expressed in many cancer cell lines and human tumors. Although several studies have addressed the role for Pak4 in transformation of fibroblasts, most human cancers are epithelial in origin. Epithelial cancers are associated not only with changes in cell growth but also with changes in the cellular organization within the three-dimensional (3D) architecture of the affected tissues. In this study we used immortalized mouse mammary epithelial cells (iMMECs) as a model system to study the role for Pak4 in mammary tumorigenesis. iMMECs are an excellent model system for studying breast cancer, as they can grow in 3D-epithelial cell culture, in which they form acinar structures that recapitulate in vivo mammary morphogenesis. Although Pak4 is expressed at low levels in wild-type iMMECs, it is overexpressed in response to oncogenes, such as oncogenic Ras and Her2/neu. In this study we found that overexpression of Pak4 in iMMECs leads to changes in 3D acinar architecture that are consistent with oncogenic transformation. These include decreased central acinar cell death, abrogation of lumen formation, cell polarity alterations and deregulation of acinar size and cell number. Furthermore, iMMECs overexpressing Pak4 form tumors when implanted into the fat pads of athymic mice. Our results suggest that overexpression of Pak4 triggers events that are important for the transformation of mammary epithelial cells. This is likely to be owing to the ability of Pak4 to inhibit apoptosis and promote cell survival and thus subsequent uncontrolled proliferation, and to its ability to deregulate cell shape and polarity.
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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.