ArticleMolecular endocrinology (Baltimore, Md.)2010
Activation of Rac1 is closely related to androgen-independent cell proliferation of prostate cancer cells both in vitro and in vivo.
Article in Molecular endocrinology (Baltimore, Md.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- The role of microRNA in castration-resistant prostate cancer.Urologic oncology · 2014Pooled it
- Targeting protein geranylgeranylation slows tumor development in a murine model of prostate cancer metastasis.Cancer biology & therapy · 2017Trial
- Newly developed preclinical models reveal broad-spectrum CDK inhibitors as potent drugs for CRPC exhibiting primary resistance to enzalutamide.Cancer science · 2024Article
- Comprehensive genomics in androgen receptor-dependent castration-resistant prostate cancer identifies an adaptation pathway mediated by opioid receptor kappa 1.Communications biology · 2022Article
- Androgen deprivation‑induced OPHN1 amplification promotes castration‑resistant prostate cancer.Oncology reports · 2022Article
- Review
- Article
- MicroRNAs in treatment-induced neuroendocrine differentiation in prostate cancer.Cancer drug resistance (Alhambra, Calif.) · 2020Article
- Systematic chemical screening identifies disulfiram as a repurposed drug that enhances sensitivity to cisplatin in bladder cancer: a summary of preclinical studies.British journal of cancer · 2019Article
- RAC2 acts as a prognostic biomarker and promotes the progression of clear cell renal cell carcinoma.International journal of oncology · 2019Article
- Androgen receptor: what we know and what we expect in castration-resistant prostate cancer.International urology and nephrology · 2018Review
- IRS-2 deubiquitination by USP9X maintains anchorage-independent cell growth via Erk1/2 activation in prostate carcinoma cell line.Oncotarget · 2018Article
- The role of Rac in tumor susceptibility and disease progression: from biochemistry to the clinic.Biochemical Society transactions · 2018Review
- p66Shc regulates migration of castration-resistant prostate cancer cells.Cellular signalling · 2018Article
- Role of MicroRNAs in Treatment Response in Prostate Cancer.Current cancer drug targets · 2018Review
- CXCL13 is androgen-responsive and involved in androgen induced prostate cancer cell migration and invasion.Oncotarget · 2017Article
- Article
- Lipin-1 regulates cancer cell phenotype and is a potential target to potentiate rapamycin treatment.Oncotarget · 2015Article
- Atypical protein kinase Cι as a human oncogene and therapeutic target.Biochemical pharmacology · 2014Review
- Regulation of onco and tumor suppressor MiRNAs by mTORC1 inhibitor PRP-1 in human chondrosarcoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We and others previously showed that signaling through cSrc or atypical protein kinase C (aPKC) pathway regulates the proliferation of prostate cancer cells and is associated with their progression to castrate-resistance in vivo. However, the interrelation of these two kinases has been largely unexplored. In the present study, we show that androgen-induced activation of cSrc regulates the activity of aPKC through the small molecular weight G protein Rac1 in androgen-dependent LNCaP cells. Knockdown of cSrc in those cells reduces the phosphorylation of aPKC and the abundance of activated form of Rac1. Additionally, the treatment of those cells with Rac1 inhibitor repressed cell cycle progression at G(1)/S transition. In fact, forced expression of a constitutively active Rac1 mutant in LNCaP cells promoted cell proliferation under androgen-depleted conditions both in vitro and in vivo. Moreover, LNCaP C4-2 and AILNCaP cells, the syngeneic androgen-independent sublines from LNCaP cells, harbored abundant Rac1-GTP. Importantly, the inhibition of Rac1 suppressed cell proliferation and induced apoptotic cell death in all prostate cancer cell lines tested irrespective of their androgen-dependence. In immunohistochemical evaluation of tumor specimens from prostate cancer patients, Rac1 pathway appeared to be activated in the majority of castrate-resistant diseases. Collectively, our present results both in vitro and in vivo highly implicate that Rac1 can be a potential therapeutic target for patients with advanced prostate cancer, especially those with castrate-resistant status.
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