ArticleCancer research2016
Synergistic Activation of ERα by Estrogen and Prolactin in Breast Cancer Cells Requires Tyrosyl Phosphorylation of PAK1.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 26 citations in OpenAlex.
- Role of serine/threonine phosphatases 1 and 2A in pancreatic acinar fluid and electrolyte secretion.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Clinical manifestation and pathological changes of serous papillary adenofibroma: A case series.Molecular and clinical oncology · 2025Article
- The immunotoxin targeting PRLR increases tamoxifen sensitivity and enhances the efficacy of chemotherapy in breast cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- Prolactin-activated PAK1 potentiates estrogen response to breast cancer cell epithelial-mesenchymal transition, migration and invasion.microPublication biology · 2024Article
- Prolactin-induced tyrosyl phosphorylation of PAK1 facilitates epithelial-mesenchymal transition.microPublication biology · 2024Article
- Review
- Review
- Identification of Signatures of Selection for Litter Size and Pubertal Initiation in Two Sheep Populations.Animals : an open access journal from MDPI · 2022Article
- Group I PAKs in myelin formation and repair of the central nervous system: what, when, and how.Biological reviews of the Cambridge Philosophical Society · 2022Review
- Prolactin receptor gene transcriptional control, regulatory modalities relevant to breast cancer resistance and invasiveness.Frontiers in endocrinology · 2022Review
- The SH2 domain and kinase activity of JAK2 target JAK2 to centrosome and regulate cell growth and centrosome amplification.PloS one · 2022Article
- Epigenetic Reprogramming of the Glucose Metabolic Pathways by the Chromatin Effectors During Cancer.Sub-cellular biochemistry · 2022Article
- Prolactin receptor signaling: A novel target for cancer treatment - Exploring anti-PRLR signaling strategies.Frontiers in endocrinology · 2022Review
- Review
- Coordinated dysregulation of cancer progression by the HER family and p21-activated kinases.Cancer metastasis reviews · 2020Review
- ERα, A Key Target for Cancer Therapy: A Review.OncoTargets and therapy · 2020Review
- P21-Activated Kinase 1: Emerging biological functions and potential therapeutic targets in Cancer.Theranostics · 2020Review
- Insights into how phosphorylation of estrogen receptor at serine 305 modulates tamoxifen activity in breast cancer.Molecular and cellular endocrinology · 2019Review
- ERα and ERβ co-expression: An indicator of aggressive tumors and hormonal sensitivity.Oncology letters · 2017Article
- Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Serine/threonine kinase PAK1 is activated by estrogen and plays an important role in breast cancer. However, the integration of PAK1 into the estrogen response is not fully understood. In this study, we investigated the mechanisms underlying the hormone-induced activation of estrogen receptor (ERα, ESR1). We show that estrogen activated PAK1 through both the ERα and GPER1 membrane receptors. Estrogen-dependent activation of PAK1 required the phosphorylation of tyrosine residues by Etk/Bmx and protein kinase A (PKA) within an assembled signaling complex comprising pTyr-PAK1, Etk/Bmx, the heterotrimer G-protein subunits Gβ1, Gγ2, and/or Gγ5, PAK-associated guanine nucleotide exchange factor (βPIX, ARHGEF7), and PKA. Moreover, the PKA RIIβ subunit is a direct target of PAK1, and thus in response to estrogen, the activated pTyr-PAK1 complex reciprocally potentiated PKA activity, suggesting a positive feedback mechanism. We also demonstrate that PKA phosphorylated Ser305-ERα in response to estrogen, but pTyr-PAK1 phosphorylated Ser305-ERα in response to prolactin (PRL), implying that maximal ERα phosphorylation is achieved when cells are exposed to both PRL and estrogen. Furthermore, S305-ERα activation led to enhanced phosphorylation of Ser118-ERα and promoted cell proliferation and tumor growth. Together, these data strongly support a critical interplay between PRL and estrogen via PAK1 and suggest that ligand-independent activation of ERα through PRL/PAK1 may impart resistance to anti-estrogen therapies. Cancer Res; 76(9); 2600-11. ©2016 AACR.
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