ArticleThe Journal of biological chemistry2013
A new signaling pathway (JAK-Fes-phospholipase D) that is enhanced in highly proliferative breast cancer cells.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Sphingosine 1-phosphate (S1P) signaling in glioblastoma multiforme-A systematic review.International journal of molecular sciences · 2017Pooled it
- Exploring druggable targets and inflammation-mediated pathways in cancer: a Mendelian randomization analysis integrating transcriptomic and proteomic data.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Immunophenotype-associated gene signature in ductal breast tumors varies by receptor subtype, but the expression of individual signature genes remains consistent.Cancer medicine · 2021Article
- PLD1 and PLD2 differentially regulate the balance of macrophage polarization in inflammation and tissue injury.Journal of cellular physiology · 2021Article
- Phospholipase Signaling in Breast Cancer.Advances in experimental medicine and biology · 2021Review
- Increased phospholipase D activity contributes to tumorigenesis in prostate cancer cell models.Molecular and cellular biochemistry · 2020Article
- Mammalian phospholipase D: Function, and therapeutics.Progress in lipid research · 2020Review
- Comparing atmospheric and hypoxic cultured mesenchymal stem cell transcriptome: implication for stem cell therapies targeting intervertebral discs.Journal of translational medicine · 2018Article
- Two sites of action for PLD2 inhibitors: The enzyme catalytic center and an allosteric, phosphoinositide biding pocket.Biochimica et biophysica acta · 2015Article
- Phospholipase D signaling pathways and phosphatidic acid as therapeutic targets in cancer.Pharmacological reviews · 2014Review
- Cellular and physiological roles for phospholipase D1 in cancer.The Journal of biological chemistry · 2014Review
- Phospholipase D in cell signaling: from a myriad of cell functions to cancer growth and metastasis.The Journal of biological chemistry · 2014Review
- Phosphatidic acid, phospholipase D and tumorigenesis.Advances in biological regulation · 2014Article
- Sustained activation of protein kinase C induces delayed phosphorylation and regulates the fate of epidermal growth factor receptor.PloS one · 2013Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The products of the oncogene Fes and JAK3 are tyrosine kinases, whose expressions are elevated in tumor growth, angiogenesis, and metastasis. Phosphatidic acid, as synthesized by phospholipase D (PLD), enhances cancer cell survival. We report a new signaling pathway that integrates the two kinases with the lipase. A new JAK3-Fes-PLD2 axis is responsible for the highly proliferative phenotype of MDA-MB-231 breast cancer cells. Conversely, this pathway is maintained at a low rate of expression and activity levels in untransformed cells such as MCF10A. We also deciphered the inter-regulation that exists between the two kinases (JAK3 and the oncogene Fes) and between these two kinases and the lipase (PLD2). Whereas JAK3 and Fes marginally activate PLD2 in non-transformed cells, these kinases greatly enhance (>200%) PLD activity following protein-protein interaction through the SH2 domain and the Tyr-415 residue of PLD2. We also found that phosphatidic acid enhances Fes activity in MDA-MB-231 cells providing a positive activation loop between Fes and PLD2. In summary, the JAK3, Fes and PLD2 interactions in transformed cells maintain PLD2 at an enhanced level that leads to abnormal cell growth. Modulating this new JAK3-Fes-PLD2 pathway could be important to control the highly invasive phenotype of breast cancer cells.
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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.