Metabolomic Profiling Reveals a Role for Androgen in Activating Amino Acid Metabolism and Methylation in Prostate Cancer Cells
Vasu, Vihas T.
Vareed, Shaiju K.
Sana, Theodore R.
Fischer, Steven M.
Palapattu, Ganesh S.
Creighton, Chad J.
MetadataShow full item record
AbstractProstate cancer is the second leading cause of cancer related death in American men. Development and progression of clinically localized prostate cancer is highly dependent on androgen signaling. Metastatic tumors are initially responsive to anti-androgen therapy, however become resistant to this regimen upon progression. Genomic and proteomic studies have implicated a role for androgen in regulating metabolic processes in prostate cancer. However, there have been no metabolomic profiling studies conducted thus far that have examined androgen-regulated biochemical processes in prostate cancer. Here, we have used unbiased metabolomic profiling coupled with enrichment-based bioprocess mapping to obtain insights into the biochemical alterations mediated by androgen in prostate cancer cell lines. Our findings indicate that androgen exposure results in elevation of amino acid metabolism and alteration of methylation potential in prostate cancer cells. Further, metabolic phenotyping studies confirm higher flux through pathways associated with amino acid metabolism in prostate cancer cells treated with androgen. These findings provide insight into the potential biochemical processes regulated by androgen signaling in prostate cancer. Clinically, if validated, these pathways could be exploited to develop therapeutic strategies that supplement current androgen ablative treatments while the observed androgen-regulated metabolic signatures could be employed as biomarkers that presage the development of castrate-resistant prostate cancer.
CitationPLoS One. 2011 Jul 18; 6(7):e21417
- Metabolomic profiling for the identification of novel diagnostic markers in prostate cancer.
- Authors: Lucarelli G, Rutigliano M, Galleggiante V, Giglio A, Palazzo S, Ferro M, Simone C, Bettocchi C, Battaglia M, Ditonno P
- Issue date: 2015
- Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression.
- Authors: Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM
- Issue date: 2009 Feb 12
- Androgen-responsive and nonresponsive prostate cancer cells present a distinct glycolytic metabolism profile.
- Authors: Vaz CV, Alves MG, Marques R, Moreira PI, Oliveira PF, Maia CJ, Socorro S
- Issue date: 2012 Nov
- Androgens regulate prostate cancer cell growth via an AMPK-PGC-1α-mediated metabolic switch.
- Authors: Tennakoon JB, Shi Y, Han JJ, Tsouko E, White MA, Burns AR, Zhang A, Xia X, Ilkayeva OR, Xin L, Ittmann MM, Rick FG, Schally AV, Frigo DE
- Issue date: 2014 Nov 6
- "Topological significance" analysis of gene expression and proteomic profiles from prostate cancer cells reveals key mechanisms of androgen response.
- Authors: Vellaichamy A, Dezso Z, JeBailey L, Chinnaiyan AM, Sreekumar A, Nesvizhskii AI, Omenn GS, Bugrim A
- Issue date: 2010 Jun 3
Showing items related by title, author, creator and subject.
Rhabdomyosarcomas in Aging A/J MiceSher, Roger B.; Cox, Gregory A.; Mills, Kevin D.; Sundberg, John P.; McNeil, Paul L.; Department of Cellular Biology and Anatomy; College of Graduate Studies (2011-08-10)Rhabdomyosarcomas (RSCs) are skeletal muscle neoplasms found in humans and domestic mammals. The A/J inbred strain developed a high frequency (between 70â 80%) of adult pleomorphic type (APT) RSC at >20 months of age while BALB/cByJ also develop RSC but less frequently. These neoplasms invaded skeletal muscle surrounding either the axial or proximal appendicular skeleton and were characterized by pleomorphic cells with abundant eosinophilic cytoplasm, multiple nuclei, and cross striations. The diagnosis was confirmed by detection of alpha-sarcomeric actin and myogenin in the neoplastic cells using immunocytochemistry. The A/J strain, but not the related BALB/c substrains, is also characterised by a progressive muscular dystrophy homologous to limb-girdle muscular dystrophy type 2B. The association between the development of RSC in similar muscle groups to those most severely affected by the progressive muscular dystrophy suggested that these neoplasms developed from abnormal regeneration of the skeletal muscle exacerbated by the dysferlin mutation. Transcriptome analyses of RSCs revealed marked downregulation of genes in muscular development and function signaling networks. Non-synonymous coding SNPs were found in Myl1, Abra, Sgca, Ttn, and Kcnj12 suggesting these may be important in the pathogenesis of RSC. These studies suggest that A strains of mice can be useful models for dissecting the molecular genetic basis for development, progression, and ultimately for testing novel anticancer therapeutic agents dealing with rhabdomyosarcoma.
The Beeper [1999 Vol. 9, No. 11]Seigler, Peggy; Baker, Toni; Steele, Deborah; Simkins, Sally L.; Simkins, Sally L.; Division of Institutional Relations; Division of Strategic Support (Medical College of Georgia, 1999-06-03)Features this week include: MCG Children's Medical Center to fill airwaves; ID badge conversion nears completion; Tollison chair receives "distinguished" designation; MCG participates in international breast cancer reduction study; Relay for Life draws supporter from throughout campus; First dental CD due this Fall; Testing may affect computer systems; Toxin may take away tightness and pain; Dr. Ellison receives Hardman Cup; Support groups offer help for cancer patients; UAB professor to address symposium; Commissions, committees appointed to study MCG future; Ultrasound enhances pregnancy care; Calcium important part of diet; Counseling available for faculty and staff; P.A. students participate in health fair; Are you at risk for Stroke?; Diabetes isn't 'same old disease'; Special collections room hold history.
Rac1 Activation Driven by 14-3-3f Dimerization Promotes Prostate Cancer Cell-Matrix Interactions, Motility and Transendothelial MigrationGoc, Anna; Abdalla, Maha; Al-Azayzih, Ahmad; Somanath, Payaningal R.; Department of Medicine (2012-07-13)14-3-3 proteins are ubiquitously expressed dimeric adaptor proteins that have emerged as key mediators of many cell signaling pathways in multiple cell types. Its effects are mainly mediated by binding to selective phosphoserine/threonine proteins. The importance of 14-3-3 proteins in cancer have only started to become apparent and its exact role in cancer progression as well as the mechanisms by which 14-3-3 proteins mediate cancer cell function remain unknown. While protein 14-3-3s is widely accepted as a tumor suppressor, 14-3-3f, b and c isoforms have been shown to have tumor promoting effects. Despite the importance of 14-3-3 family in mediating various cell processes, the exact role and mechanism of 14-3-3f remain unexplored. In the current study, we investigated the role of protein 14-3-3f in prostate cancer cell motility and transendothelial migration using biochemical, molecular biology and electric cell-substrate impedance sensing approaches as well as cell based functional assays. Our study indicated that expression with wild-type protein 14-3-3f significantly enhanced Rac activity in PC3 cells. In contrast, expression of dimer-resistant mutant of protein 14-3-3f (DM-14-3-3) inhibited Rac activity and associated phosphorylation of p21 activated kinase-1 and 2. Expression with wild-type 14-3-3f or constitutively active Rac1 enhanced extracellular matrix recognition, lamellipodia formation, cell migration and trans-endothelial migration by PC3 cells. In contrast, expression with DM 14-3-3f or DN-Rac1 in PC3 cells significantly inhibited these cell functions. Our results demonstrate for the first time that 14-3-3f enhances prostate cancer cell-matrix interactions, motility and transendothelial migration in vitro via activation of Rac1-GTPase and is an important target for therapeutic interventions for prostate cancer.