{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T02:41:51Z","timestamp":1768444911147,"version":"3.49.0"},"reference-count":105,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T00:00:00Z","timestamp":1726099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT","award":["UIDB\/04501\/2020"],"award-info":[{"award-number":["UIDB\/04501\/2020"]}]},{"name":"FCT","award":["SFRH\/BD\/146032\/2019"],"award-info":[{"award-number":["SFRH\/BD\/146032\/2019"]}]},{"name":"FCT","award":["COVID\/BD\/153457\/2023"],"award-info":[{"award-number":["COVID\/BD\/153457\/2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Protein phosphatase 1 (PP1) complexes have emerged as promising targets for anticancer therapies. The ability of peptides to mimic PP1-docking motifs, and so modulate interactions with regulatory factors, has enabled the creation of highly selective modulators of PP1-dependent cellular processes that promote tumor growth. The major objective of this study was to develop a novel bioactive cell-penetrating peptide (bioportide), which, by mimicking the PP1-binding motif of caveolin-1 (CAV1), would regulate PP1 activity, to hinder prostate cancer (PCa) progression. The designed bioportide, herein designated CAVPENET, and a scrambled homologue, were synthesized using microwave-assisted solid-phase methodologies and evaluated using PCa cell lines. Our findings indicate that CAVPENET successfully entered PCa cells to influence both viability and migration. This tumor suppressor activity of CAVPENET was attributed to inhibition of AKT signaling, a consequence of increased PP1\u03b3 activity. This led to the suppression of glycolytic metabolism and alteration in lipid metabolism, collectively representing the primary mechanism responsible for the anticancer properties of CAVPENET. Our results underscore the potential of the designed peptide as a novel therapy for PCa patients, setting the stage for further testing in more advanced models to fully realize its therapeutic promise.<\/jats:p>","DOI":"10.3390\/pharmaceutics16091199","type":"journal-article","created":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T06:31:40Z","timestamp":1726122700000},"page":"1199","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["CAVPENET Peptide Inhibits Prostate Cancer Cells Proliferation and Migration through PP1\u03b3-Dependent Inhibition of AKT Signaling"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9570-1819","authenticated-orcid":false,"given":"B\u00e1rbara","family":"Matos","sequence":"first","affiliation":[{"name":"Laboratory of Signal Transduction, Department of Medical Sciences, iBiMED-Institute of Biomedicine, University of Aveiro, 3810-193 Aveiro, Portugal"},{"name":"Cancer Biology and Epigenetics Group, IPO Porto Research Center (CI-IPOP), RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"given":"Antoniel A. S.","family":"Gomes","sequence":"additional","affiliation":[{"name":"Department of Biophysics & Pharmacology, Institute of Biosciences of Botucatu, S\u00e3o Paulo State University, Botucatu 18610-034, SP, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1941-6634","authenticated-orcid":false,"given":"Raquel","family":"Bernardino","sequence":"additional","affiliation":[{"name":"Unit for Multidisciplinary Research in Biomedicine (UMIB), School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Rua Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Laboratory for Integrative and Translational Research in Population Health (ITR), 4050-600 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7635-783X","authenticated-orcid":false,"given":"Marco G.","family":"Alves","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, iBiMED-Institute of Biomedicine, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"given":"John","family":"Howl","sequence":"additional","affiliation":[{"name":"Faculty of Health, Education and Life Sciences, Birmingham City University, Edgbaston, Birmingham B15 3TN, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4186-5345","authenticated-orcid":false,"given":"Carmen","family":"Jer\u00f3nimo","sequence":"additional","affiliation":[{"name":"Cancer Biology and Epigenetics Group, IPO Porto Research Center (CI-IPOP), RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Department of Pathology and Molecular Immunology, ICBAS-School of Medicine and Biomedical Sciences, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7459-9173","authenticated-orcid":false,"given":"Margarida","family":"Fardilha","sequence":"additional","affiliation":[{"name":"Laboratory of Signal Transduction, Department of Medical Sciences, iBiMED-Institute of Biomedicine, University of Aveiro, 3810-193 Aveiro, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,12]]},"reference":[{"key":"ref_1","unstructured":"Ferlay, J., Ervik, M., Lam, F., Laversanne, M., Colombet, M., Mery, L., Pi\u00f1eros, M., Znaor, A., Soerjomataram, I., and Bray, F. (2024, March 11). Global Cancer Observatory: Cancer Today. International Agency for Research on Cancer. Available online: https:\/\/gco.iarc.who.int\/today."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Felgueiras, J., Jer\u00f3nimo, C., and Fardilha, M. (2020). Protein phosphatase 1 in tumorigenesis: Is it worth a closer look?. Biochim. Biophys. Acta Rev. Cancer, 1874.","DOI":"10.1016\/j.bbcan.2020.188433"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.cell.2009.10.006","article-title":"Serine\/Threonine Phosphatases: Mechanism through Structure","volume":"139","author":"Shi","year":"2009","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.tibs.2010.03.002","article-title":"The extended PP1 toolkit: Designed to create specificity","volume":"35","author":"Bollen","year":"2010","journal-title":"Trends Biochem. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.jmb.2008.10.053","article-title":"Crystal Structures of Protein Phosphatase-1 Bound to Nodularin-R and Tautomycin: A Novel Scaffold for Structure-based Drug Design of Serine\/Threonine Phosphatase Inhibitors","volume":"385","author":"Kelker","year":"2009","journal-title":"J. Mol. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2680","DOI":"10.1016\/j.drudis.2021.08.001","article-title":"Modulation of serine\/threonine-protein phosphatase 1 (PP1) complexes: A promising approach in cancer treatment","volume":"26","author":"Matos","year":"2021","journal-title":"Drug Discov. Today"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9389","DOI":"10.1128\/MCB.23.24.9389-9404.2003","article-title":"Caveolin-1 Maintains Activated Akt in Prostate CancerCells through Scaffolding Domain Binding Site Interactions with andInhibition of Serine\/Threonine Protein Phosphatases PP1 andPP2A","volume":"23","author":"Li","year":"2003","journal-title":"Mol. Cell. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"D\u00edaz-Valdivia, N., Sim\u00f3n, L., D\u00edaz, J., Martinez-Meza, S., Contreras, P., Burgos-Ravanal, R., P\u00e9rez, V.I., Frei, B., Leyton, L., and Quest, A.F.G. (2022). Mitochondrial Dysfunction and the Glycolytic Switch Induced by Caveolin-1 Phosphorylation Promote Cancer Cell Migration, Invasion, and Metastasis. Cancers, 14.","DOI":"10.3390\/cancers14122862"},{"key":"ref_9","first-page":"935","article-title":"A selective inhibitor of elF2\u03b1 dephosphorylation protects cells from ER stress","volume":"307","author":"Boyce","year":"2005","journal-title":"Science (1979)"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7685","DOI":"10.1074\/jbc.M310997200","article-title":"Deactylase Inhibitors Disrupt Cellular Complexes Containing Protein Phosphatases and Deacetylases","volume":"279","author":"Brush","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.drudis.2017.10.016","article-title":"Interfering peptides targeting protein\u2013protein interactions: The next generation of drugs?","volume":"23","author":"Alezra","year":"2018","journal-title":"Drug Discov. Today"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10054","DOI":"10.1002\/anie.201204308","article-title":"Development of a Peptide that Selectively Activates Protein Phosphatase-1 in Living Cells","volume":"51","author":"Chatterjee","year":"2012","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1021\/acs.joc.9b02548","article-title":"Development of a Photoactivatable Protein Phosphatase-1-Disrupting Peptide","volume":"85","author":"Trebacz","year":"2020","journal-title":"J. Org. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1002\/cbic.201800541","article-title":"Interrogating PP1 Activity in the MAPK Pathway with Optimized PP1-Disrupting Peptides","volume":"20","author":"Wang","year":"2019","journal-title":"ChemBioChem"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s00395-019-0720-7","article-title":"Protein kinase\/phosphatase balance mediates the effects of increased late sodium current on ventricular calcium cycling","volume":"114","author":"Eiringhaus","year":"2019","journal-title":"Basic Res. Cardiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1113\/JP278951","article-title":"Activation of endogenous protein phosphatase 1 enhances the calcium sensitivity of the ryanodine receptor type 2 in murine ventricular cardiomyocytes","volume":"598","author":"Potenza","year":"2020","journal-title":"J. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1002\/ejhf.1297","article-title":"Activation of protein phosphatase 1 by a selective phosphatase disrupting peptide reduces sarcoplasmic reticulum Ca2+ leak in human heart failure","volume":"20","author":"Fischer","year":"2018","journal-title":"Eur. J. Heart Fail."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3971","DOI":"10.4161\/cc.8.23.10191","article-title":"Disruption of the PP1\/GADD34 complex induces calreticulin exposure","volume":"8","author":"Kepp","year":"2009","journal-title":"Cell Cycle"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.cub.2010.01.020","article-title":"Repo-Man Controls a Protein Phosphatase 1-Dependent Threshold for DNA Damage Checkpoint Activation","volume":"20","author":"Peng","year":"2010","journal-title":"Curr. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2693","DOI":"10.1158\/1535-7163.MCT-09-0228","article-title":"Anticancer activity of targeted proapoptotic peptides and chemotherapy is highly improved by targeted cell surface calreticulin-inducer peptides","volume":"8","author":"Obeid","year":"2009","journal-title":"Mol. Cancer Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1080\/14737140.2022.2139679","article-title":"Lutetium Lu 177 vipivotide tetraxetan for metastatic castration-resistant prostate cancer","volume":"22","author":"Shah","year":"2022","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.tips.2017.01.003","article-title":"Cell-Penetrating Peptides: From Basic Research to Clinics","volume":"38","author":"Guidotti","year":"2017","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e24154","DOI":"10.1002\/pep2.24154","article-title":"A new biology of cell penetrating peptides","volume":"113","author":"Howl","year":"2021","journal-title":"Pept. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.coph.2019.03.014","article-title":"Bioactive cell penetrating peptides and proteins in cancer: A bright future ahead","volume":"47","author":"Jauset","year":"2019","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1124\/mol.105.019364","article-title":"Use of penetrating peptides interacting with PP1\/PP2A proteins as a general approach for a drug phosphatase technology","volume":"69","author":"Guergnon","year":"2006","journal-title":"Mol. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"10444","DOI":"10.1016\/S0021-9258(17)34080-2","article-title":"The third helix of the Antennapedia homeodomain translocates through biological membranes","volume":"269","author":"Derossi","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Patel, S.G., Sayers, E.J., He, L., Narayan, R., Williams, T.L., Mills, E.M., Allemann, R.K., Luk, L.Y.P., Jones, A.T., and Tsai, Y.-H. (2019). Cell-penetrating peptide sequence and modification dependent uptake and subcellular distribution of green florescent protein in different cell lines. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-42456-8"},{"key":"ref_28","first-page":"1377","article-title":"Microwave assisted peptide synthesis of some rationally designed cell penetrating peptides from c-kit receptor","volume":"62","author":"Osman","year":"2019","journal-title":"Egypt. J. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10989-018-9681-1","article-title":"A High-Throughput Synthetic Platform Enables the Discovery of Proteomimetic Cell Penetrating Peptides and Bioportides","volume":"25","author":"Jones","year":"2019","journal-title":"Int. J. Pept. Res. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Evans, R., O\u2019neill, M., Pritzel, A., Antropova, N., Senior, A., Green, T., \u017d\u00eddek, A., Bates, R., Blackwell, S., and Yim, J. (2022). Protein complex prediction with AlphaFold-Multimer. bioRxiv.","DOI":"10.1101\/2021.10.04.463034"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"Gromacs: High performance molecular simulations through multi-level parallelism from laptops to supercomputers","volume":"1\u20132","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/nmeth.4067","article-title":"CHARMM36m: An improved force field for folded and intrinsically disordered proteins","volume":"14","author":"Huang","year":"2016","journal-title":"Nat. Methods"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1021\/ct100578z","article-title":"PROPKA3: Consistent treatment of internal and surface residues in empirical p K a predictions","volume":"7","author":"Olsson","year":"2011","journal-title":"J. Chem. Theory Comput."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1002\/jcc.20945","article-title":"CHARMM-GUI: A web-based graphical user interface for CHARMM","volume":"29","author":"Jo","year":"2008","journal-title":"J. Comput. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"014101","DOI":"10.1063\/1.2408420","article-title":"Canonical sampling through velocity rescaling","volume":"126","author":"Bussi","year":"2007","journal-title":"J. Chem. Phys."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7182","DOI":"10.1063\/1.328693","article-title":"Polymorphic transitions in single crystals: A new molecular dynamics method","volume":"52","author":"Parrinello","year":"1981","journal-title":"J. Appl. Phys."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: Visual Molecular Dynamics","volume":"14","author":"Humphrey","year":"1996","journal-title":"J. Mol. Graph."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6408","DOI":"10.1073\/pnas.91.14.6408","article-title":"Phosphorylation and Inactivation of Protein Phosphatase 1 by Cyclin-Dependent Kinases (Cel Cyck\/Protein IhIsphor-Ltln\/it\/-Dc Mutagens)","volume":"91","author":"Dohadwala","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","first-page":"7777","article-title":"The Heat Shock Protein 90 Inhibitor Geldanamycin and the ErbB Inhibitor ZD1839 Promote Rapid PP1 Phosphatase-Dependent Inactivation of AKT in ErbB2 Overexpressing Breast Cancer Cells","volume":"63","author":"Xu","year":"2003","journal-title":"Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1002\/ijc.22862","article-title":"Activation of PI3K-Akt signaling pathway promotes prostate cancer cell invasion","volume":"121","author":"Shukla","year":"2007","journal-title":"Int. J. Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"11960","DOI":"10.1073\/pnas.220413597","article-title":"Phosphorylation and Inactivation of Glycogen Synthase Kinase 3 by Protein Kinase A","volume":"97","author":"Fang","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1002\/cbic.202000669","article-title":"Towards Dissecting the Mechanism of Protein Phosphatase-1 Inhibition by Its C-Terminal Phosphorylation","volume":"22","author":"Salvi","year":"2021","journal-title":"ChemBioChem"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"113282","DOI":"10.1016\/j.yexcr.2022.113282","article-title":"PP1 catalytic isoforms are differentially expressed and regulated in human prostate cancer","volume":"418","author":"Felgueiras","year":"2022","journal-title":"Exp. Cell Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/0014-5793(93)80889-3","article-title":"Cantharidin, another natural toxin that inhibits the activity of serine\/threonine protein phosphatases types 1 and 2A","volume":"330","author":"Honkanen","year":"1993","journal-title":"FEBS Lett."},{"key":"ref_45","first-page":"280","article-title":"Downregulation of c-FLIP and upregulation of DR-5 by cantharidin sensitizes TRAIL-mediated apoptosis in prostate cancer cells via autophagy flux","volume":"46","author":"Nazim","year":"2020","journal-title":"Int. J. Mol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Goo, C.K., Lim, H.Y., Ho, Q.S., Too, H.P., Clement, M.V., and Wong, K.P. (2012). PTEN\/Akt Signaling Controls Mitochondrial Respiratory Capacity through 4E-BP1. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0045806"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Fontana, F., Anselmi, M., and Limonta, P. (2022). Exploiting the Metabolic Consequences of PTEN Loss and Akt\/Hexokinase 2 Hyperactivation in Prostate Cancer: A New Role for \u03b4-Tocotrienol. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23095269"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e210","DOI":"10.1038\/emm.2015.116","article-title":"Resveratrol augments ER stress and the cytotoxic effects of glycolytic inhibition in neuroblastoma by downregulating Akt in a mechanism independent of SIRT1","volume":"48","author":"Graham","year":"2016","journal-title":"Exp. Mol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Schmidt, C.A., Fisher-Wellman, K.H., and Darrell Neufer, P. (2021). From OCR and ECAR to energy: Perspectives on the design and interpretation of bioenergetics studies. J. Biol. Chem., 297.","DOI":"10.1016\/j.jbc.2021.101140"},{"key":"ref_50","first-page":"e54918","article-title":"An optimized protocol to analyze glycolysis and mitochondrial respiration in lymphocytes","volume":"2016","author":"Traba","year":"2016","journal-title":"J. Vis. Exp."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1101\/gad.889901","article-title":"Inhibition of early apoptotic events by Akt\/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase","volume":"15","author":"Gottlob","year":"2001","journal-title":"Genes Dev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1158\/1535-7163.MCT-14-0183","article-title":"Lipid catabolism via CPT1 as a therapeutic target for prostate cancer","volume":"13","author":"Schlaepfer","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1042\/CS20190587","article-title":"Fatty acid oxidation inhibitor etomoxir suppresses tumor progression and induces cell cycle arrest via PPAR\u03b3-mediated pathway in bladder cancer","volume":"133","author":"Cheng","year":"2019","journal-title":"Clin. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Li, J., Gong, C., Zhou, H., Liu, J., Xia, X., Ha, W., Jiang, Y., Liu, Q., and Xiong, H. (2024). Kinase Inhibitors and Kinase-Targeted Cancer Therapies: Recent Advances and Future Perspectives. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25105489"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1007\/s10495-015-1141-1","article-title":"Inflammation-induced radioresistance is mediated by ROS-dependent inactivation of protein phosphatase 1 in non-small cell lung cancer cells","volume":"20","author":"Kim","year":"2015","journal-title":"Apoptosis"},{"key":"ref_56","first-page":"389","article-title":"Calyculin A induces apoptosis and stimulates phosphorylation of p65NF-kappaB in human osteoblastic osteosarcoma MG63 cells","volume":"31","author":"Tanaka","year":"2007","journal-title":"Int. J. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"120","DOI":"10.5497\/wjp.v3.i4.120","article-title":"Phosphoprotein phosphatase 1-interacting proteins as therapeutic targets in prostate cancer","volume":"3","author":"Felgueiras","year":"2014","journal-title":"World J. Pharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/pcan.2009.29","article-title":"The role of caveolin-1 in prostate cancer: Clinical implications","volume":"13","author":"Thompson","year":"2010","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1039\/C8NR10447F","article-title":"Membrane potential drives direct translocation of cell-penetrating peptides","volume":"11","author":"Gao","year":"2019","journal-title":"Nanoscale"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"109945","DOI":"10.1016\/j.celrep.2021.109945","article-title":"The endocytic pathway taken by cationic substances requires Rab14 but not Rab5 and Rab7","volume":"37","author":"Trofimenko","year":"2021","journal-title":"Cell Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1016\/j.bbamem.2014.04.025","article-title":"A proapoptotic peptide conjugated to penetratin selectively inhibits tumor cell growth","volume":"1838","author":"Alves","year":"2014","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e24037","DOI":"10.1002\/pep2.24037","article-title":"Preparation and cellular uptake of bicyclic-peptide cargo clicked to cell penetrating peptides","volume":"110","author":"Kulkarni","year":"2018","journal-title":"Pept. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1152\/ajpcell.00458.2004","article-title":"Caveolin-1 in oncogenic transformation, cancer, and metastasis","volume":"288","author":"Williams","year":"2005","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_64","first-page":"4272","article-title":"In Situ Prostate Cancer Gene Therapy Using a Novel Adenoviral Vector Regulated by the Caveolin-1 Promoter 1","volume":"7","author":"Pramudji","year":"2001","journal-title":"Clin. Cancer Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1080\/15384101.2019.1618118","article-title":"Deletion of caveolin scaffolding domain alters cancer cell migration","volume":"18","author":"Okada","year":"2019","journal-title":"Cell Cycle"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S1535-6108(03)00168-5","article-title":"Selective Inhibition of Tumor Microvascular Permeability by Cavtratin Blocks Tumor Progression in Mice","volume":"4","author":"Gratton","year":"2003","journal-title":"Cancer Cell"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"6525","DOI":"10.1074\/jbc.272.10.6525","article-title":"Identification of Peptide and Protein Ligands for the Caveolin-Scaffolding: Domain Implications for the Interaction of Caveolin with Caveolae-Associated Proteins","volume":"272","author":"Couet","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"819","DOI":"10.2147\/OTT.S123912","article-title":"The different functions and clinical significances of caveolin-1 in human adenocarcinoma and squamous cell carcinoma","volume":"10","author":"Fu","year":"2017","journal-title":"Onco Targets Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"53407","DOI":"10.1074\/jbc.M403775200","article-title":"Inhibition of Akt kinase activity by a peptide spanning the \u03b2A strand of the proto-oncogene TCL1","volume":"279","author":"Hiromura","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1002\/ijc.24424","article-title":"Targeting AKT with the proapoptotic peptide, TAT-CTMP: A novel strategy for the treatment of human pancreatic adenocarcinoma","volume":"125","author":"Simon","year":"2009","journal-title":"Int. J. Cancer"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.bbrc.2022.04.054","article-title":"A novel self-assemble peptide drug design of AKT1 for anaplastic thyroid cancer therapy","volume":"611","author":"Chai","year":"2022","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.2174\/0113895575270904231129062137","article-title":"Targeted Inhibition of the PI3K\/Akt\/mTOR Signaling Axis: Potential for Sarcoma Therapy","volume":"24","author":"Wani","year":"2024","journal-title":"Mini-Rev. Med. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s11010-010-0544-0","article-title":"Regulation of GSK3 isoforms by phosphatases PP1 and PP2A","volume":"344","author":"Langa","year":"2010","journal-title":"Mol. Cell. Biochem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1002\/jcb.23033","article-title":"Protein phosphatase 1-dependent dephosphorylation of Akt is the prime signaling event in sphingosine-induced apoptosis in Jurkat cells","volume":"112","author":"Thayyullathil","year":"2011","journal-title":"J. Cell. Biochem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"28874","DOI":"10.1074\/jbc.M703472200","article-title":"Structural basis for regulation of protein phosphatase 1 by inhibitor-2","volume":"282","author":"Hurley","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1016\/j.str.2019.07.012","article-title":"Flexible Tethering of ASPP Proteins Facilitates PP-1c Catalysis","volume":"27","author":"Zhou","year":"2019","journal-title":"Structure"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1096\/fj.07-092841","article-title":"Selective targeting of the \u03b31 isoform of protein phosphatase 1 to F-actin in intact cells requires multiple domains in spinophilin and neurabin","volume":"22","author":"Carmody","year":"2008","journal-title":"FASEB J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1083\/jcb.200508154","article-title":"Repo-Man recruits PP1\u03b3 to chromatin and is essential for cell viability","volume":"172","author":"Andersen","year":"2006","journal-title":"J. Cell Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1089\/omi.2011.0041","article-title":"Protein phosphatase 1\u03b1 interacting proteins in the human brain","volume":"16","author":"Esteves","year":"2012","journal-title":"OMICS A J. Integr. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"67","DOI":"10.4236\/jbpc.2014.52008","article-title":"Phosphoprotein Phosphatase 1 Isoforms Alpha and Gamma Respond Differently to Prodigiosin Treatment and Present Alternative Kinase Targets in Melanoma Cells","volume":"05","author":"Fardilha","year":"2014","journal-title":"J. Biophys. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1038\/nature04209","article-title":"Towards a proteome-scale map of the human protein-protein interaction network","volume":"437","author":"Rual","year":"2005","journal-title":"Nature"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Cutruzzol\u00e0, F., Giardina, G., Marani, M., Macone, A., Paiardini, A., Rinaldo, S., and Paone, A. (2017). Glucose metabolism in the progression of prostate cancer. Front. Physiol., 8.","DOI":"10.3389\/fphys.2017.00097"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4896","DOI":"10.1158\/0008-5472.CAN-21-2647","article-title":"Cancer signaling drives cancer metabolism: AKT and the Warburg effect","volume":"81","author":"Hosios","year":"2021","journal-title":"Cancer Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.bbrc.2015.06.092","article-title":"PI3K\/Akt signaling mediated Hexokinase-2 expression inhibits cell apoptosis and promotes tumor growth in pediatric osteosarcoma","volume":"464","author":"Zhuo","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"343","DOI":"10.3892\/mmr.2021.11982","article-title":"HK2 is associated with the Warburg effect and proliferation in liver cancer: Targets for effective therapy with glycyrrhizin","volume":"23","author":"Sun","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s12935-016-0280-y","article-title":"Inhibition of glycolytic enzyme hexokinase II (HK2) suppresses lung tumor growth","volume":"16","author":"Wang","year":"2016","journal-title":"Cancer Cell Int."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e32213","DOI":"10.7554\/eLife.32213","article-title":"Selective eradication of cancer displaying hyperactive Akt by exploiting the metabolic consequences of Akt activation","volume":"7","author":"Nogueira","year":"2018","journal-title":"eLife"},{"key":"ref_88","first-page":"1181","article-title":"Licochalcone A suppresses hexokinase 2-mediated tumor glycolysis in gastric cancer via downregulation of the Akt signaling pathway","volume":"39","author":"Wu","year":"2018","journal-title":"Oncol. Rep."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Le Grand, M., Berges, R., Pasquier, E., Montero, M.-P., Borge, L., Carrier, A., Vasseur, S., Bourgarel, V., Buric, D., and Andr\u00e9, N. (2017). Akt targeting as a strategy to boost chemotherapy efficacy in non-small cell lung cancer through metabolism suppression. Sci. Rep., 7.","DOI":"10.1038\/srep45136"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1158\/1535-7163.MCT-14-0888","article-title":"The PI3K\/Akt pathway regulates oxygen metabolism via pyruvate dehydrogenase (PDH)-E1\u03b1 phosphorylation","volume":"14","author":"Cerniglia","year":"2015","journal-title":"Mol. Cancer Ther."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Siltari, A., Syv\u00e4l\u00e4, H., Lou, Y.R., Gao, Y., and Murtola, T.J. (2022). Role of Lipids and Lipid Metabolism in Prostate Cancer Progression and the Tumor\u2019s Immune Environment. Cancers, 14.","DOI":"10.3390\/cancers14174293"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"7324","DOI":"10.1074\/jbc.M109.035584","article-title":"Akt and c-Myc differentially activate cellular metabolic programs and prime cells to bioenergetic inhibition","volume":"285","author":"Fan","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"37372","DOI":"10.1074\/jbc.M608372200","article-title":"Phosphatidylinositol 3-kinase-dependent modulation of carnitine palmitoyltransferase 1A expression regulates lipid metabolism during hematopoietic cell growth","volume":"281","author":"DeBerardinis","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"113450","DOI":"10.1016\/j.fct.2022.113450","article-title":"Apoptosis induction in human prostate cancer cells related to the fatty acid metabolism by wogonin-mediated regulation of the AKT-SREBP1-FASN signaling network","volume":"169","author":"Sun","year":"2022","journal-title":"Food Chem. Toxicol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.2147\/CMAR.S236301","article-title":"Free fatty acids promote the development of prostate cancer by upregulating peroxisome proliferator-activated receptor gamma","volume":"12","author":"Ha","year":"2020","journal-title":"Cancer Manag. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"3666","DOI":"10.1038\/s41388-020-1243-2","article-title":"Lipogenic signalling modulates prostate cancer cell adhesion and migration via modification of Rho GTPases","volume":"39","author":"Manuelli","year":"2020","journal-title":"Oncogene"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1080\/21541248.2020.1826781","article-title":"Exploring a role for fatty acid synthase in prostate cancer cell migration","volume":"12","author":"Manuelli","year":"2021","journal-title":"Small GTPases"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1038\/labinvest.2008.97","article-title":"Overexpression of fatty acid synthase is associated with palmitoylation of Wnt1 and cytoplasmic stabilization of \u03b2-catenin in prostate cancer","volume":"88","author":"Fiorentino","year":"2008","journal-title":"Lab. Investig."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"120046","DOI":"10.1016\/j.lfs.2021.120046","article-title":"Palmitic acid inhibits prostate cancer cell proliferation and metastasis by suppressing the PI3K\/Akt pathway","volume":"286","author":"Zhu","year":"2021","journal-title":"Life Sci."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Drury, J., Rychahou, P.G., He, D., Jafari, N., Wang, C., Lee, E.Y., Weiss, H.L., Evers, B.M., and Zaytseva, Y.Y. (2020). Inhibition of Fatty Acid Synthase Upregulates Expression of CD36 to Sustain Proliferation of Colorectal Cancer Cells. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.01185"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/s41419-021-03596-w","article-title":"The fatty acid receptor CD36 promotes HCC progression through activating Src\/PI3K\/AKT axis-dependent aerobic glycolysis","volume":"12","author":"Luo","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Joshi, M., Kim, J., D\u2019alessandro, A., Monk, E., Bruce, K., Elajaili, H., Nozik-Grayck, E., Goodspeed, A., Costello, J.C., and Schlaepfer, I.R. (2020). CPT1A over-expression increases reactive oxygen species in the mitochondria and promotes antioxidant defenses in prostate cancer. Cancers, 12.","DOI":"10.3390\/cancers12113431"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"56051","DOI":"10.18632\/oncotarget.17359","article-title":"Lipid Catabolism Inhibition Sensitizes Prostate Cancer Cells to Antiandrogen Blockade","volume":"8","author":"Flaig","year":"2017","journal-title":"Oncotarget"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1042\/CS20060307","article-title":"A double-blind randomised, multicentre clinical trial to evaluate the efficacy and safety of two doses of etomoxir in comparison with placebo in patients with moderate congestive heart failure: The ERGO (etomoxir for the recovery of glucose oxidation) study","volume":"113","author":"Holubarsch","year":"2007","journal-title":"Clin. Sci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1593\/neo.07817","article-title":"Caveolin-1 mediated expression and secretion of Kallikrein 6 in colon cancer cells","volume":"10","author":"Henkhaus","year":"2008","journal-title":"Neoplasia"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/9\/1199\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:54:36Z","timestamp":1760111676000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/9\/1199"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,12]]},"references-count":105,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["pharmaceutics16091199"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics16091199","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,12]]}}}