Publications

See the full list on pubmed

2025

  • Structural basis for LZTR1 recognition of RAS GTPases for degradation

    Dharmaiah S*, Bonsor DA*, Mo S*, Fernandez-Cabrera A, Chan AH, Messing S, Drew M, Vega M, Nissley DV, Esposito D, Castel P*, Simanshu DK* Science 389 (6765), 1112-1117

    DOI: 10.1126/science.adv7088

  • RIT1 drives oncogenic transformation and is an actionable target in lung adenocarcinoma

    Mozzarelli AM, Cuevas-Navarro A, Shuldiner EG, Vega M, Chatila WK, Xu J, Walch HS, Niu Y, Petrov DA, Schultz N, Urisman A, Rudin CM, Winslow MM, Castel P Cancer Research 85 (17), 3196-3206

    DOI: 10.1158/0008-5472.CAN-24-3819

    Our work was also featured on the cover of Vol 85, Issue 17 of Cancer Research!

    (See commentary)

2024

  • Functional and structural insights into RAS effector proteins

    Mozzarelli AM, Simanshu DM, Castel P Molecular Cell 84 (15), 2807-2821

    DOI: 10.1016/j.molcel.2024.06.027

  • The Noncanonical RAS/MAPK Pathway and the RASopathies

    Mo S, Castel P. Chapter in Rauen, K.A. (eds) “The RASopathies”. Springer Nature Link. 427-456.

    DOI: 10.1007/978-3-031-62945-7_19

  • Methylation of the chromatin modifier KMT2D by SMYD2 contributes to therapeutic response in hormone-dependent breast cancer

    Blawski R, Vokshi BH, Guo X, Kittane S, Sallaku M, Chen W, Gjyzari M, Cheung T, Zhang Y, Simpkins C, Zhou C, Kulick A, Zhao P, Wei M, Shivashankar P, Prioleau T, Razavi P, Koche R, Rebecca VW, de Stanchina E, Castel P, Chan HM, Scaltriti M, Cocco E, Ji H, Luo M, Toska E Cell Reports 43 (5).

    DOI: 10.1016/j.celrep.2024.114174 

  • The deubiquitinase USP9X regulates RIT1 protein abundance and oncogenic phenotypes

    Riley AK, Grant M, Snell A, Cromwell E, Vichas A, Moorthi S, Rominger C, Modukuri SP, Urisman A, Castel P, Wan L, Berger AH Iscience 27 (8)

    DOI: 10.1016/j.isci.2024.110499 

2023

  • RAS-dependent RAF-MAPK hyperactivation by pathogenic RIT1 is a therapeutic target in Noonan syndrome–associated cardiac hypertrophy

    Cuevas-Navarro A, Wagner M, Van R, Swain M, Mo S, Columbus J, Allison MR, Cheng A, Messing S, Turbyville TJ, Simanshu DK, Sale MJ, McCormick F, Stephen AG, Castel P. Science Advances 9 (28), eadf4766

    DOI: 10.1126/sciadv.adf4766

  • The ribosomal S6 kinase 2 (RSK2)–SPRED2 complex regulates the phosphorylation of RSK substrates and MAPK signaling

    Lopez J, Bonsor DA, Sale MJ, Urisman A, Mehalko JL, Cabanski-Dunning M, Castel P, Simanshu DK, McCormick F. Journal of Biological Chemistry 299 (6)

    DOI: 10.1016/j.jbc.2023.104789 

  • Papillomas of Costello syndrome are not associated with human papillomavirus infection in a small case series

    Olsen GM, Johnson L, Castel P, Stevenson DA, White K, Chiu YE, Krol A, Siegel DH. Journal of the American Academy of Dermatology 89 (2), 385-388

    DOI: 10.1016/j.jaad.2023.03.043 

  • Impaired Proteolysis of Noncanonical RAS Proteins Drives Clonal Hematopoietic Transformation

    Chen S, Vedula RS, Cuevas-Navarro A, Lu B, Hogg SJ, Wang E, Benbarche S, Knorr K, Kim WJ, Stanley RF, Cho H, Erickson C, Singer M, Cui D, Tittley S, Durham BH, Pavletich TS, Fiala E, Walsh MF, Inoue D, Monette S, Taylor J, Rosen N, McCormick F, Lindsley RC, Castel P, Abdel-Wahab O. Cancer Discovery 12 (10), 2434-2453

    DOI:10.1158/2159-8290.CD-21-1631

2022

  • Cross-species analysis of LZTR1 loss-of-function mutants demonstrates dependency to RIT1 orthologs

    Cuevas-Navarro A, Rodriguez-Muñoz L, Grego-Bessa J, Cheng A, Rauen KA, Urisman A, McCormick F, Jimenez G, Castel P. Elife 11, e76495.

    DOI: 10.7554/eLife.76495

  • Defective protein degradation in genetic disorders

    Castel P. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 1868 (5), 166366

    DOI:10.1016/j.bbadis.2022.166366

  • Impaired Proteolysis of Noncanonical RAS Proteins Drives Clonal Hematopoietic Transformation

    Chen S, Vedula RS, Cuevas-Navarro A, Lu B, Hogg SJ, Wang E, Benbarche S, Knorr K, Kim WJ, Stanley RF, Cho H, Erickson C, Singer M, Cui D, Tittley S, Durham BH, Pavletich TS, Fiala E, Walsh MF, Inoue D, Monette S, Taylor J, Rosen N, McCormick F, Lindsley RC, Castel P, Abdel-Wahab O. Cancer Discovery 12 (10), 2434-2453

    DOI:10.1158/2159-8290.CD-21-1631

  • Noncanonical function of Capicua as a growth termination signal in Drosophila oogenesis

    Rodríguez-Muñoz L, Lagares C, González-Crespo S, Castel P, Veraksa A, Jiménez G. Proceedings of the National Academy of Sciences 119 (31), e2123467119

    DOI: 10.1073/pnas.2123467119

  • The oncogenic PI3K-induced transcriptomic landscape reveals key functions in splicing and gene expression regulation

    Ladewig E, Michelini F, Jhaveri K, Castel P, Carmona J, Fairchild L, Zuniga AG, Arruabarrena-Aristorena A, Cocco E, Blawski R, Kittane S, Zhang Y, Sallaku M, Baldino L, Hristidis V, Chandarlapaty S, Abdel-Wahab O, Leslie C, Scaltriti M, Toska E. Cancer Research 82 (12), 2269-2280

    DOI: 10.1158/0008-5472.CAN-22-0446

  • Angiocrine polyamine production regulates adiposity

    Monelli E, Villacampa P, Zabala-Letona A, Martinez-Romero A, Llena J, Beiroa D, Gouveia L, Chivite I, Zagmutt S, Gama-Perez P, Osorio-Conles O, Muixi. L, Martinez-Gonzalez A, Castillo SD, Martin-Martin N, Castel P, Valcarcel-Jimenez L, Garcia-Gonzalez I, Villena JA, Fernandez-Ruiz S, Serra D, Herrero L, Benedito R, Garcia-Roves P, Vidal J, Cohen P, Nogueiras R, Claret M, Carracedo A, Graupera M. Nature Metabolism 4 (3), 327-343.

    DOI: 10.1038/s42255-022-00544-6

2021

  • The present and future of PI3K inhibitors for cancer therapy

    Castel P, Toska E, Engelman JA, Scaltriti M. Nature Cancer 2, 587–597.

    DOI: 10.1038/s43018-021-00218-4

  • The RAS GTPase RIT1 compromises mitotic fidelity through spindle assembly checkpoint suppression

    Cuevas-Navarro A, Van R, Cheng A, Urisman A, Castel P, McCormick F. Current Biology 31 (17), 3915-3924. e9

    DOI: 10.1016/j.cub.2021.06.030 

  • RAS interaction with Sin1 is dispensable for mTORC2 assembly and activity

    Castel P, Dharmaiah S, Sale MJ, Messing S, Rizzuto G, Cuevas-Navarro A, Cheng A, Trnka MJ, Urisman A, Esposito D, Simanshu DK, McCormick F

    DOI: 10.1073/pnas.210326111

  • DoMY-Seq: A yeast two-hybrid–based technique for precision mapping of protein–protein interaction motifs

    Castel P, Holtz-Morris A, Kwon Y, Suter BP, McCormick F. Journal of Biological Chemistry 296.

    DOI: 10.1074/jbc.RA120.014284 External Link

  • Impaired RAS Proteolysis Drives Clonal Hematopoietic Transformation

    Chen S, Vedula RS, Castel P, Cuevas Navarro A, Hogg SJ, Wang E, Mi X, Benbarche S, Knorr K, Kim WJ, Cho H, Erickson C, Singer ME, Cui D, Durham B, Inoue D, Monette S, Rosen N, McCormick F, Lindsley Jr RC, Abdel-Wahab O. Blood 138, 356.

    DOI: 10.1182/blood-2021-147026

  • Minor intron retention drives clonal hematopoietic disorders and diverse cancer predisposition

    Inoue. D, Polaski JT, Taylor J, Castel P, Chen S, Kobayashi S, Hogg SJ, Hayashi Y, Pineda JMB, El Marabti E, Erickson C, Knorr K, Fukumoto M, Yamazaki H, Tanaka A, Fukui C, Lu SX, Durham BH, Liu B, Wang E, Mehta S, Zakheim D, Garippa R, Penson A, Chew GL, McCormick F, Bradley RK, Abdel-Wahab O. Nature Genetics 53 (5), 707-718.

    DOI: 10.1038/s41588-021-00828-9

  • Genomic Alterations in PIK3CA-Mutated Breast Cancer Result in mTORC1 Activation and Limit the Sensitivity to PI3Kα Inhibitors

    Cai Y, Xu G, Wu F, Michelini F, Chan C, Qu X, Selenica P, Ladewig E, Castel P, Cheng Y, Zhao A, Jhaveri K, Toska E, Jimenez M, Jacquet A, Tran-Dien A, Andre F, Chandarlapaty S, Reis-Filho JS, Razavi P, Scaltriti M. Cancer Research 81 (9), 2470-2480.

    DOI: 10.1158/0008-5472.CAN-20-3232

2020

  • The duality of human oncoproteins: drivers of cancer and congenital disorders

    Castel P, Rauen KA, McCormick F. Nature Reviews Cancer 20 (7), 383-397.

    DOI: 10.1038/s41568-020-0256-z

  • A novel vascular tumour characterized by coexisting HRAS and GNAQ activating mutations

    Castel P, Bagué S, Granell E, Guerrero Vara R, Baselga J, Baselga E. British Journal of Dermatology 180 (4), 927-928.

    DOI: 10.1111/bjd.17393

  • PI3K inhibition activates SGK1 via a feedback loop to promote chromatin-based regulation of ER-dependent gene expression

    Toska E, Castel P, Chhangawala S, Arruabarrena-Aristorena A, Chan C, Hristidis VC, Cocco E, Sallaku M, Xu G, Park J, Minuesa G, Shifman SG, Socci ND, Koche R, Leslie CS, Scaltriti M, Baselga J. Cell Reports 27 (1), 294-306. e5

    DOI: 10.1016/j.celrep.2019.02.111

  • ZRSR2 Mutation Induced Minor Intron Retention Drives MDS and Diverse Cancer Predisposition Via Aberrant Splicing of LZTR1

    Inoue D, Polaski JT, Taylor J, Castel P, Chen S, Kobayashi S, Hogg SJ, Hayashi Y, Pineda JMB, Penson AV, El Marabti E, Erickson C, Fukumoto M, Yamazaki H, Fukui C, Lu SX, Durham BH, Liu B, Mehta S, Zakheim D, Garippa R, Chew GL, McCormick F, Bradley RK, Abdel-Wahab O. Blood 136, 10-11

    DOI: 10.1182/blood-2020-136445

  • KrasP34R and KrasT58I mutations induce distinct RASopathy phenotypes in mice

    Wong JC, Perez-Mancera PA, Huang TQ, Kim J, Grego-Bessa J, Alzamora MDP, Kogan SC, Sharir A, Keefe SH, Morales CE, Schanze D, Castel P, Hirose K, Huang GN, Zenker M, Sheppard D, Klein OD, Tuveson DA, Braun BS, Shannon K. JCI insight 5 (21), e140495.

    DOI: 10.1172/jci.insight.140495

  • The molecular functions of RIT1 and its contribution to human disease

    Van R, Cuevas-Navarro A, Castel P, McCormick F. Biochemical Journal 477 (15), 2755-2770

    DOI: 10.1042/BCJ20200442

2019

  • RIT1 oncoproteins escape LZTR1-mediated proteolysis

    Castel P, Cheng A, Cuevas-Navarro A, Everman DB, Papageorge AG, Simanshu DK, Tankka A, Galeas J, Urisman A, McCormick F. Science 363 (6432), 1226-1230.

    DOI: 10.1126/science.aav1444

  • PI3K inhibition activates SGK1 via a feedback loop to promote chromatin-based regulation of ER-dependent gene expression

    Toska E, Castel P, Chhangawala S, Arruabarrena-Aristorena A, Chan C, Hristidis VC, Cocco E, Sallaku M, Xu G, Park J, Minuesa G, Shifman SG, Socci ND, Koche R, Leslie CS, Scaltriti M, Baselga J. Cell Reports 27 (1), 294-306. e5

    DOI: 10.1016/j.celrep.2019.02.111

  • A novel vascular tumour characterized by coexisting HRAS and GNAQ activating mutations

    Castel P, Bagué S, Granell E, Guerrero Vara R, Baselga J, Baselga E. British Journal of Dermatology 180 (4), 927-928.

    DOI: 10.1111/bjd.17393

  • EGFR and MET Amplifications Determine Response to HER2 Inhibition in ERBB2-Amplified Esophagogastric Cancer

    Sanchez-Vega F, Hechtman JF, Castel P, Ku GY, Tuvy Y, Won H, Fong CJ, Bouvier N, Nanjangud GJ, Soong, Vakiani E, Schattner M, Kelsen DP, Lefkowitz RA, Brown K, Lacouture ME, Capanu M, Mattar M, Qeriqi B, Cecchi F, Tian Y, Hembrough T, Nagy RJ, Lanman RB, Larson SM, Pandit-Taskar N, Schöder N, Jacobuzio-Donahue CA, Ilson DH, Weber WA, Berger MF, De Stanchina E, Taylor BS, Lewis JS, Solit DB, Carrasquillo JA, Scaltriti M, Schultz N, Janjigian YY. Cancer Discovery 9 (2), 199-209.

    DOI: 10.1158/2159-8290.CD-18-0598

  • Chromatin regulation at the intersection of estrogen receptor and PI3K pathways in breast cancer

    Castel P, Toska E. Molecular & Cellular Oncology 6 (6), e1625620

    DOI: 10.1080/23723556.2019.1625620

  • Endothelial cell rearrangements during vascular patterning require PI3-kinase-mediated inhibition of actomyosin contractility

    Angulo-Urarte A, Casado P, Castillo SD, Kobialka P, Kotini MP, Figueiredo AM, Castel P, Rajeeve V, Milà-Guasch M, Millan J, Wiesner C, Serra H, Muixi L, Casanovas O, Viñals F, Affolter M, Gerhardt H, Huveneers S, Belting HG, Cutillas PR, Graupera M. Nature Communications, 9 (1), 4826.

    DOI: 10.1038/s41467-018-07172-3

2018

  • Somatic PIK3CA mutations as a driver of sporadic venous malformations

    Castel P, Carmona FJ, Grego-Bessa J, Berger MF, Viale. A, Anderson KV, Bague S, Scaltriti M, Antonescu CR, Baselga E, Baselga J. Science Translational Medicine 10 (466).

    DOI: 10.1126/scitranslmed.aaf1164

  • Endothelial cell rearrangements during vascular patterning require PI3-kinase-mediated inhibition of actomyosin contractility

    Angulo-Urarte A, Casado P, Castillo SD, Kobialka P, Kotini MP, Figueiredo AM, Castel P, Rajeeve V, Milà-Guasch M, Millan J, Wiesner C, Serra H, Muixi L, Casanovas O, Viñals F, Affolter M, Gerhardt H, Huveneers S, Belting HG, Cutillas PR, Graupera M. Nature Communications, 9 (1), 4826.

    DOI: 10.1038/s41467-018-07172-3

  • Mechanisms of Resistance to PI3K and AKT Inhibitors

    Castel P, Scaltriti M. Chapter in: Yarden, Y., Elkabets, M. (eds) Resistance to Anti-Cancer Therapeutics Targeting Receptor Tyrosine Kinases and Downstream Pathways. Resistance to Targeted Anti-Cancer Therapeutics, vol 15. Springer, Cham.

    DOI: 10.1007/978-3-319-67932-7_6

2017

  • PI3K pathway regulates ER-dependent transcription in breast cancer through the epigenetic regulator KMT2D

    Toska E, Osmanbeyoglu HU, Castel P, Chan C, Hendrickson RC, Elkabets M, Dickler MN, Scaltriti M, Leslie CS, Armstrong SA, Baselga J. Science 355 (6331), 1324-1330.

    DOI: 10.1126/science.aah6893

2016

  • PDK1-SGK1 Signaling Sustains AKT-Independent mTORC1 Activation and Confers Resistance to PI3Kα Inhibition

    Castel P, Ellis H, Bago R, Toska E, Razavi P, Carmona FJ, Kannan S, Verma CS, Dickler M, Chandarlapaty S, Brogi E, Alessi DR, Baselga J, Scaltriti M. Cancer Cell 30 (2), 229-242.

    DOI: 10.1016/j.ccell.2016.06.004 

  • Somatic PIK3CA mutations as a driver of sporadic venous malformations

    Castel P, Carmona FJ, Grego-Bessa J, Berger MF, Viale A, Anderson KV, Bague S, Scaltriti M, Antonescu CR, Baselga E, Baselga J. Science Translational Medicine 8 (332), 332ra42-332ra42.

    DOI: 10.1126/scitranslmed.aaf1164

  • Therapeutic Benefit of Selective Inhibition of p110α PI3-Kinase in Pancreatic Neuroendocrine Tumors

    Soler A, Figueiredo AM, Castel P, Martin L, Monelli E, Angulo-Urarte A, Milà-Guasch M, Viñals F, Baselga J, Casanovas O, Graupera M. Clinical Cancer Research 22 (23), 5805-5817.

    DOI: 10.1158/1078-0432.CCR-15-3051

  • PIM1 kinase regulates cell death, tumor growth and chemotherapy response in triple-negative breast cancer

    Brasó-Maristany F, Filosto S, Catchpole S, Marlow R, Quist J, Francesch-Domenech E, Plumb DA, Zakka L, Gazinska P, Liccardi G, Meier P, Gris-Oliver A, Cheang MCU, Perdrix-Rosell A, Shafat M, Noël E, Patel N, McEachern K, Scaltriti M, Castel P, Noor F, Buus R, Mathew S, Watkins J, Serra V, Marra P, Grigoriadis A, Tutt AN. Nature Medicine, 22 (11), 1303-1313.

    DOI: 10.1038/nm.4198

  • Systematic functional characterization of resistance to PI3K inhibition in breast cancer

    Le X, Antony R, Razavi P, Treacy DJ, Luo F, Ghandi M, Castel P, Scaltriti M, Baselga J, Garraway LA. Cancer Discovery 6 (10), 1134-1147.

    DOI: 10.1158/2159-8290.CD-16-0305

  • The hVps34‐SGK 3 pathway alleviates sustained PI3K/Akt inhibition by stimulating mTORC 1 and tumour growth

    Bago R, Sommer E, Castel P, Crafter C, Bailey FP, Shpiro N, Baselga J, Cross D, Eyers PA, Alessi DR. The EMBO Journal 35 (17), 1902-1922.

    DOI: 10.15252/embj.201693929

  • The tumor suppressor PTEN and the PDK1 kinase regulate formation of the columnar neural epithelium

    Grego-Bessa J, Bloomekatz J, Castel P, Omelchenko T, Baselga J, Anderson KV. Elife 5, e12034.

    DOI: 10.7554/eLife.12034

2015

  • Therapeutic Benefit of Selective Inhibition of p110α PI3-Kinase in Pancreatic Neuroendocrine Tumors

    Juric D, Castel P, Griffith M, Griffith OL, Won H, Ellis H, Ebbesen SH, Ainscough BJ, Ramu A, Iyer G, Shah RH, Huynh T, Mino-Kenudson M, Sgroi D, Isakoff S, Thabet A, Elamine L, Solit DB, Lowe SW, Quadt C, Peters M, Derti A, Schegel R, Huang A, Mardis ER, Berger MF, Baselga J, Scaltriti M. Nature 518 (7538), 240-244.

    DOI: 10.1038/nature13948

  • PI3K inhibition results in enhanced estrogen receptor function and dependence in hormone receptor–positive breast cancer

    Bosch A, Li Z, Bergamaschi A, Ellis H, Toska E, Prat A, Tao JJ, Spratt DE, Viola-Villegas NT, Castel P, Minuesa G, Morse N, Rodón J, Ibrahim Y, Cortes J, Perez-Garcia J, Galvan P, Grueso J, Guzman M, Katzenellenbogen JA, Kharas M, Lewis JS, Dickler M, Serra V, Rosen N, Chandarlapaty S, Scaltriti M, Baselga J. Science Translational Medicine 7 (283), 283ra51-283ra51.

    DOI: 10.1126/scitranslmed.aaa4442