ArticleCellular signalling2012
Protein kinase A-mediated phosphorylation of RhoA on serine 188 triggers the rapid induction of a neuroendocrine-like phenotype in prostate cancer epithelial cells.
Article in Cellular signalling, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Actomyosin-mediated inhibition of synaptic vesicle release under CBTranslational psychiatry · 2024Article
- Revisiting the roles of cAMP signalling in the progression of prostate cancer.The Biochemical journal · 2023Article
- Article
- Histone lysine demethylase KDM4B regulates the alternative splicing of the androgen receptor in response to androgen deprivation.Nucleic acids research · 2019Article
- Effect of A549 neuroendocrine differentiation on cytotoxic immune response.Endocrine connections · 2018Article
- cAMP-dependent regulation of RhoA/Rho-kinase attenuates detrusor overactivity in a novel mouse experimental model.BJU international · 2017Article
- Arg188 drives RhoC membrane binding.Small GTPases · 2017Article
- Inhibition of Uterine Contractility by Thalidomide Analogs via Phosphodiesterase-4 Inhibition and Calcium Entry Blockade.Molecules (Basel, Switzerland) · 2016Article
- Triiodothyronine Attenuates Prostate Cancer Progression Mediated by β-Adrenergic Stimulation.Molecular medicine (Cambridge, Mass.) · 2016Article
- β-Adrenergic Receptor Signaling in Prostate Cancer.Frontiers in oncology · 2014Review
- Phosphorylation-mediated regulation of GEFs for RhoA.Cell adhesion & migration · 2014Review
- The protein kinase A regulatory subunit R1A (Prkar1a) plays critical roles in peripheral nerve development.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Role of nuclear receptor NR4A2 in gastrointestinal inflammation and cancers.World journal of gastroenterology · 2012Article
- Beta-adrenergic signaling on neuroendocrine differentiation, angiogenesis, and metastasis in prostate cancer progression.Asian journal of andrologyReview
- Rho GTPase regulation of reactive oxygen species generation and signalling in platelet function and disease.Small GTPasesReview
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Whilst androgen ablation therapy is used to treat locally advanced or metastatic forms of prostate cancer, side-effects can include the emergence of an androgen-independent neuroendocrine cell population which is associated with poor prognosis. Here we have examined how cyclic AMP elevation regulates early events in the neuroendocrine differentiation process. We demonstrate that selective activation of protein kinase A is necessary and sufficient for cyclic AMP (cAMP) elevation to rapidly promote a neuroendocrine phenotype in LNCaP cells independent of de novo protein synthesis. Furthermore, the effects of cAMP could be recapitulated by inhibition of RhoA signalling or pharmacological inhibition of Rho kinase. Conversely, expression of constitutively active Gln63Leu-mutated RhoA acted as a dominant-negative inhibitor of cAMP-mediated NE phenotype formation. Consistent with these observations, cAMP elevation triggered the PKA-dependent phosphorylation of RhoA on serine 188, and a non-phosphorylatable Ser188Ala RhoA mutant functioned as a dominant-negative inhibitor of cAMP-mediated neuroendocrine phenotype formation. These results suggest that PKA-mediated inhibition of RhoA via its phosphorylation on serine 188 and the subsequent inhibition of ROCK activity plays a key role in determining initial changes in cellular morphology during LNCaP cell differentiation to a neuroendocrine phenotype. It also raises the possibility that targeted suppression of this pathway to inhibit neuroendocrine cell expansion might be a useful adjuvant to conventional prostate cancer therapy.
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