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fatty acid binding prostate cancer

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https://www.readbyqxmd.com/read/28415688/inhibitor-sbfi26-suppresses-the-malignant-progression-of-castration-resistant-pc3-m-cells-by-competitively-binding-to-oncogenic-fabp5
#1
Waseem Al-Jameel, Xiaojun Gou, Shiva S Forootan, Majed Saad Al Fayi, Philip S Rudland, Farzad S Forootan, Jiacheng Zhang, Philip A Cornford, Syed A Hussain, Youqiang Ke
Castration resistant-prostate cancer is largely impervious to feather hormonal therapy and hence the outlook for patients is grim. Here we use an approach to attach the recently discovered Achilles heel. The experimental treatment established in this study is based on the recent discovery that it is the FABP5-PPARγ-VEGF signalling axis, rather than the androgen receptor pathway, played a dominant role in promoting the malignant progression of castration resistant prostate cancer cells. Treatments have been established in mice by suppressing the biological activity of FABP5 using a chemical inhibitor SBFI26...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28387458/anti-tumorigenic-potential-of-a-novel-orlistat-aicar-combination-in-prostate-cancer-cells
#2
Clayton Wright, Anand Krishnan V Iyer, Vivek Kaushik, Neelam Azad
Prostate cancer (PCa) is one of the leading causes of cancer-related deaths in men worldwide. Fatty acid synthase (FASN) is reported to be overexpressed in several cancers including PCa, and this has led to clinical cancer treatments that utilize various FASN inhibitors such as the anti-obesity drug, Orlistat. However, pharmacological limitations have impeded the progress in cancer treatments expected thus far with FASN inhibition. In this study, we investigated a novel therapeutic combination to enhance the toxic potential of Orlistat in three different PCa cell-lines (DU145, PC3, and LNCaP)...
April 7, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28342983/lipid-quantification-by-raman-microspectroscopy-as-a-potential-biomarker-in-prostate-cancer
#3
Jordan O'Malley, Rahul Kumar, Andrey N Kuzmin, Artem Pliss, Neelu Yadav, Srimmitha Balachandar, Jianmin Wang, Kristopher Attwood, Paras N Prasad, Dhyan Chandra
Metastatic castration-resistant prostate cancer (mCRPC) remains incurable and is one of the leading causes of cancer-related death among American men. Therefore, detection of prostate cancer (PCa) at early stages may reduce PCa-related mortality in men. We show that lipid quantification by vibrational Raman Microspectroscopy and Biomolecular Component Analysis may serve as a potential biomarker in PCa. Transcript levels of lipogenic genes including sterol regulatory element-binding protein-1 (SREBP-1) and its downstream effector fatty acid synthase (FASN), and rate-limiting enzyme acetyl CoA carboxylase (ACACA) were upregulated corresponding to both Gleason score and pathologic T stage in the PRAD TCGA cohort...
March 23, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28211531/proteomic-analysis-of-urinary-extracellular-vesicles-from-high-gleason-score-prostate-cancer
#4
Kazutoshi Fujita, Hideaki Kume, Kyosuke Matsuzaki, Atsunari Kawashima, Takeshi Ujike, Akira Nagahara, Motohide Uemura, Yasushi Miyagawa, Takeshi Tomonaga, Norio Nonomura
Extracellular vesicles (EVs) are microvesicles secreted from various cell types. We aimed to discover a new biomarker for high Gleason score (GS) prostate cancer (PCa) in urinary EVs via quantitative proteomics. EVs were isolated from urine after massage from 18 men (negative biopsy [n = 6], GS 6 PCa [n = 6], or GS 8-9 PCa [n = 6]). EV proteins were labeled with iTRAQ and analyzed by LC-MS/MS. We identified 4710 proteins and quantified 3528 proteins in the urinary EVs. Eleven proteins increased in patients with PCa compared to those with negative biopsy (ratio >1...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28163102/the-peritumoural-adipose-tissue-microenvironment-and-cancer-the-roles-of-fatty-acid-binding-protein-4-and-fatty-acid-binding-protein-5
#5
S Guaita-Esteruelas, J Gumà, L Masana, J Borràs
The adipose tissue microenvironment plays a key role in tumour initiation and progression because it provides fatty acids and adipokines to tumour cells. The fatty acid-binding protein (FABP) family is a group of small proteins that act as intracellular fatty acid transporters. Adipose-derived FABPs include FABP4 and FABP5. Both have an important role in lipid-related metabolic processes and overexpressed in many cancers, such as breast, prostate, colorectal and ovarian. Moreover, their expression in peritumoural adipose tissue is deregulated, and their circulating levels are upregulated in some tumours...
February 3, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28049638/leukemic-blasts-program-bone-marrow-adipocytes-to-generate-a-protumoral-microenvironment
#6
Manar S Shafat, Thomas Oellerich, Sebastian Mohr, Stephen D Robinson, Dylan R Edwards, Christopher R Marlein, Rachel E Piddock, Matthew Fenech, Lyubov Zaitseva, Amina Abdul-Aziz, Jeremy Turner, Johnathan A Watkins, Matthew Lawes, Kristian M Bowles, Stuart A Rushworth
Despite currently available therapies, most patients diagnosed with acute myeloid leukemia (AML) die of their disease. Tumor-host interactions are critical for the survival and proliferation of cancer cells; accordingly, we hypothesize that specific targeting of the tumor microenvironment may constitute an alternative or additional strategy to conventional tumor-directed chemotherapy. Because adipocytes have been shown to promote breast and prostate cancer proliferation, and because the bone marrow adipose tissue accounts for up to 70% of bone marrow volume in adult humans, we examined the adipocyte-leukemia cell interactions to determine if they are essential for the growth and survival of AML...
March 9, 2017: Blood
https://www.readbyqxmd.com/read/27825431/pet-tracers-beyond-fdg-in-prostate-cancer
#7
REVIEW
David M Schuster, Cristina Nanni, Stefano Fanti
Conventional anatomical imaging with CT and MRI has limitations in the evaluation of prostate cancer. PET is a powerful imaging technique, which can be directed toward molecular targets as diverse as glucose metabolism, density of prostate-specific membrane antigen receptors, and skeletal osteoblastic activity. Although 2-deoxy-2-(18)F-FDG-PET is the mainstay of molecular imaging, FDG has limitations in typically indolent prostate cancer. Yet, there are many useful and emerging PET tracers beyond FDG, which provide added value...
November 2016: Seminars in Nuclear Medicine
https://www.readbyqxmd.com/read/27779102/the-increased-expression-of-fatty-acid-binding-protein-9-in-prostate-cancer-and-its-prognostic-significance
#8
Majed Saad Al Fayi, Xiaojun Gou, Shiva S Forootan, Waseem Al-Jameel, Zhengzheng Bao, Philip R Rudland, Philip A Cornford, Syed A Hussain, Youqiang Ke
In contrast to numerous studies conducted to investigate the crucial role of fatty acid binding protein 5 (FABP5) in prostate cancer, investigations on the possible involvement of other FABPs are rare. Here we first measured the mRNA levels of 10 FABPs in benign and malignant prostate cell lines and identified the differentially expressed FABP6 and FABP9 mRNAs whose levels in all malignant cell lines were higher than those in the benign cells. Thereafter we assessed the expression status of FABP6 and FABP9 in both prostate cell lines and in human tissues...
December 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27582526/for-better-or-worse-ffar1-and-ffar4-signaling-in-cancer-and-diabetes
#9
Julia M Houthuijzen
Increased energy intake can lead to obesity, which increases the risk for the development of diabetes and cancer. Free fatty acids regulate numerous cellular processes like insulin secretion, inflammation, proliferation and cell migration. Dysregulation of these cellular functions by increased lipid intake plays a significant role in the development of diseases like diabetes and cancer. FFAR1 and FFAR4 are two free fatty acid receptors that are under increasing investigation for their roles in diabetes and more recently also cancer...
August 31, 2016: Molecular Pharmacology
https://www.readbyqxmd.com/read/27474750/positive-and-negative-cross-talk-between-lysophosphatidic-acid-receptor-1-free-fatty-acid-receptor-4-and-epidermal-growth-factor-receptor-in-human-prostate-cancer-cells
#10
Mandi M Hopkins, Ze Liu, Kathryn E Meier
Lysophosphatidic acid (LPA) is a lipid mediator that mediates cellular effects via G protein-coupled receptors (GPCRs). Epidermal growth factor (EGF) is a peptide that acts via a receptor tyrosine kinase. LPA and EGF both induce proliferation of prostate cancer cells and can transactivate each other's receptors. The LPA receptor LPA1 is particularly important for LPA response in human prostate cancer cells. Previous work in our laboratory has demonstrated that free fatty acid 4 (FFA4), a GPCR activated by ω-3 fatty acids, inhibits responses to both LPA and EGF in these cells...
October 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27471561/proteomic-upregulation-of-fatty-acid-synthase-and-fatty-acid-binding-protein-5-and-identification-of-cancer-and-race-specific-pathway-associations-in-human-prostate-cancer-tissues
#11
Jennifer S Myers, Ariana K von Lersner, Qing-Xiang Amy Sang
Protein profiling studies of prostate cancer have been widely used to characterize molecular differences between diseased and non-diseased tissues. When combined with pathway analysis, profiling approaches are able to identify molecular mechanisms of prostate cancer, group patients by cancer subtype, and predict prognosis. This strategy can also be implemented to study prostate cancer in very specific populations, such as African Americans who have higher rates of prostate cancer incidence and mortality than other racial groups in the United States...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/26934656/p300-acetyltransferase-regulates-fatty-acid-synthase-expression-lipid-metabolism-and-prostate-cancer-growth
#12
Xiaokun Gang, Yinhui Yang, Jian Zhong, Kui Jiang, Yunqian Pan, R Jeffrey Karnes, Jun Zhang, Wanhai Xu, Guixia Wang, Haojie Huang
De novo fatty acid (FA) synthesis is required for prostate cancer (PCa) survival and progression. As a key enzyme for FA synthesis fatty acid synthase (FASN) is often overexpressed in human prostate cancers and its expression correlates with worse prognosis and poor survival. P300 is an acetyltransferase that acts as a transcription co-activator. Increasing evidence suggests that P300 is a major PCa promoter, although the underlying mechanism remains poorly understood. Here, we demonstrated that P300 binds to and increases histone H3 lysine 27 acetylation (H3K27Ac) in the FASN gene promoter...
March 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/26814431/fatty-acid-activated-ppar%C3%AE-promotes-tumorigenicity-of-prostate-cancer-cells-by-up-regulating-vegf-via-ppar-responsive-elements-of-the-promoter
#13
Farzad S Forootan, Shiva S Forootan, Xiaojun Gou, Jin Yang, Bichong Liu, Danqing Chen, Majed Saad Al Fayi, Waseem Al-Jameel, Philip S Rudland, Syed A Hussain, Youqiang Ke
In previous work, it is suggested that the excessive amount of fatty acids transported by FABP5 may facilitate the malignant progression of prostate cancer cells through a FABP5-PPARγ-VEGF signal transduction axis to increase angiogenesis. To further functionally characterise the FABP5-PPARγ-VEGF signal transduction pathway, we have, in this work, investigated the molecular mechanisms involved in its tumorigenicity promoting role in prostate cancer. Suppression of PPARγ in highly malignant prostate cancer cells produced a significant reduction (up to 53%) in their proliferation rate, invasiveness (up to 89%) and anchorage-independent growth (up to 94%) in vitro...
February 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/26614767/the-cancer-promoting-gene-fatty-acid-binding-protein-5-fabp5-is-epigenetically-regulated-during-human-prostate-carcinogenesis
#14
Koichiro Kawaguchi, Ayumi Kinameri, Shunsuke Suzuki, Shogo Senga, Youqiang Ke, Hiroshi Fujii
FABPs (fatty-acid-binding proteins) are a family of low-molecular-mass intracellular lipid-binding proteins consisting of ten isoforms. FABPs are involved in binding and storing hydrophobic ligands such as long-chain fatty acids, as well as transporting these ligands to the appropriate compartments in the cell. FABP5 is overexpressed in multiple types of tumours. Furthermore, up-regulation of FABP5 is strongly associated with poor survival in triple-negative breast cancer. However, the mechanisms underlying the specific up-regulation of the FABP5 gene in these cancers remain poorly characterized...
February 15, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/26408707/signatures-of-adverse-pathological-features-androgen-insensitivity-and-metastatic-potential-in-prostate-cancer
#15
Yuri Tolkach, Axel Merseburger, Thomas Herrmann, Markus Kuczyk, Jürgen Serth, Florian Imkamp
BACKGROUND/AIM: The genetic characterization of prostate tumors is important for personalized therapy. The aim of the present study was to investigate the role of previously described prostate cancer-related genes in the genetic characterization of prostate tumors. MATERIALS AND METHODS: Forty-two genes were selected for expression analysis (real time-quantitative polymerase chain reaction). One normal prostatic epithelial cell line and three standardized prostate cancer cell lines were used...
October 2015: Anticancer Research
https://www.readbyqxmd.com/read/26002551/metformin-induced-energy-deficiency-leads-to-the-inhibition-of-lipogenesis-in-prostate-cancer-cells
#16
Camille Loubière, Thomas Goiran, Kathiane Laurent, Zied Djabari, Jean-François Tanti, Frédéric Bost
The deregulation of lipid metabolism is a hallmark of tumor cells, and elevated lipogenesis has been reported in prostate cancer. Metformin, a drug commonly prescribed for type II diabetes, displays antitumor properties. Here, we show that metformin inhibits lipogenesis in several prostate cancer cell lines. In LNCaP cells, this effect parallels the decrease of key lipogenic proteins: ACC (acetyl-CoA carboxylase), FASN (fatty acid synthase) and SREBP1c (sterol regulatory element binding protein-1c), whereas there is no modification in DU145 and PC3 cells...
June 20, 2015: Oncotarget
https://www.readbyqxmd.com/read/25940306/salicylate-activates-ampk-and-synergizes-with-metformin-to-reduce-the-survival-of-prostate-and-lung-cancer-cells-ex-vivo-through-inhibition-of-de-novo-lipogenesis
#17
Andrew J O'Brien, Linda A Villani, Lindsay A Broadfield, Vanessa P Houde, Sandra Galic, Giovanni Blandino, Bruce E Kemp, Theodoros Tsakiridis, Paola Muti, Gregory R Steinberg
Aspirin, the pro-drug of salicylate, is associated with reduced incidence of death from cancers of the colon, lung and prostate and is commonly prescribed in combination with metformin in individuals with type 2 diabetes. Salicylate activates the AMP-activated protein kinase (AMPK) by binding at the A-769662 drug binding site on the AMPK β1-subunit, a mechanism that is distinct from metformin which disrupts the adenylate charge of the cell. A hallmark of many cancers is high rates of fatty acid synthesis and AMPK inhibits this pathway through phosphorylation of acetyl-CoA carboxylase (ACC)...
July 15, 2015: Biochemical Journal
https://www.readbyqxmd.com/read/25746209/the-effects-of-androgen-deprivation-therapy-with-weight-management-on-serum-ap2-and-adiponectin-levels-in-prostate-cancer-patients
#18
Hayato Urushima, Yukiko Inomata-Kurashiki, Kazuo Nishimura, Ryoko Sumi, Iichiro Shimomura, Norio Nonomura, Toshinori Ito, Kazuhisa Maeda
Androgen deprivation therapy (ADT) for the treatment of prostate cancer (PCa) causes an increase in total body fat, leading to a net gain in body weight. Moreover, the use of the luteinizing hormone-releasing hormone agonists in ADT causes a decrease in serum androgen levels, leading to the development of metabolic syndrome (MetS). Androgen blockade significantly increases plasma adiponectin levels, which has some efficacy against MetS, whereas ADT increases fasting plasma insulin and decreases insulin sensitivity, suggesting that there are other mechanisms involved in the onset of MetS besides adiponectin activation...
June 2015: Aging Male: the Official Journal of the International Society for the Study of the Aging Male
https://www.readbyqxmd.com/read/25720493/activated-%C3%AE-2-macroglobulin-binding-to-human-prostate-cancer-cells-triggers-insulin-like-responses
#19
Uma Kant Misra, Salvatore Vincent Pizzo
Ligation of cell surface GRP78 by activated α2-macroglobulin (α2M*) promotes cell proliferation and suppresses apoptosis. α2M*-treated human prostate cancer cells exhibit a 2-3-fold increase in glucose uptake and lactate secretion, an effect similar to insulin treatment. In both α2M* and insulin-treated cells, the mRNA levels of SREBP1-c, SREBP2, fatty-acid synthase, acetyl-CoA carboxylase, ATP citrate lyase, and Glut-1 were significantly increased together with their protein levels, except for SREBP2. Pretreatment of cells with α2M* antagonist antibody directed against the carboxyl-terminal domain of GRP78 blocks these α2M*-mediated effects, and silencing GRP78 expression by RNAi inhibits up-regulation of ATP citrate lyase and fatty-acid synthase...
April 10, 2015: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/25512540/a-long-noncoding-rna-connects-c-myc-to-tumor-metabolism
#20
Chiu-Lien Hung, Ling-Yu Wang, Yen-Ling Yu, Hong-Wu Chen, Shiv Srivastava, Gyorgy Petrovics, Hsing-Jien Kung
Long noncoding RNAs (lncRNAs) have been implicated in a variety of physiological and pathological processes, including cancer. In prostate cancer, prostate cancer gene expression marker 1 (PCGEM1) is an androgen-induced prostate-specific lncRNA whose overexpression is highly associated with prostate tumors. PCGEM1's tumorigenic potential has been recently shown to be in part due to its ability to activate androgen receptor (AR). Here, we report a novel function of PCGEM1 that provides growth advantages for cancer cells by regulating tumor metabolism via c-Myc activation...
December 30, 2014: Proceedings of the National Academy of Sciences of the United States of America
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