Evidence map›Paper›PMID 25622896›Full record

ArticleNeoplasia (New York, N.Y.)2015

Structure-function studies of the bHLH phosphorylation domain of TWIST1 in prostate cancer cells.

Rajendra P Gajula, Sivarajan T Chettiar, Russell D Williams, Katriana Nugent, Yoshinori Kato, Hailun Wang, Reem Malek, Kekoa Taparra, Jessica Cades, Anvesh Annadanam and 8 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neoplasia (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.1field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. WNT Pathway Mutations in Metachronous Oligometastatic Castration-Sensitive Prostate Cancer.International journal of radiation oncology, biology, physics · 2023
    Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. TWIST1-WDR5-Cancer research · 2017
    Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 4 institutions in 1 country.

Rajendra P GajulaDepartment of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sivarajan T ChettiarDepartment of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Russell D WilliamsDepartment of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Katriana NugentDepartment of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Yoshinori KatoThe Russell H. Morgan Department of Radiology and Radiological Science, Division of Cancer Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; In Vivo Cellular and Molecular Imaging Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Hailun WangDepartment of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Reem MalekDepartment of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Kekoa TaparraDepartment of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Cellular and Molecular Medicine Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jessica CadesDepartment of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Anvesh AnnadanamDepartment of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
A-Rum YoonDepartment of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
Elana FertigDepartment of Oncology, Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Beth A FirulliDepartment of Pediatrics, Riley Heart Research Center, Indiana University School of Medicine, Indianapolis, IN, USA.
Lucia MazzacuratiDepartment of Medicine, Division of Hematology-Oncology, Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Timothy F BurnsDepartment of Medicine, Division of Hematology-Oncology, Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Anthony B FirulliDepartment of Pediatrics, Riley Heart Research Center, Indiana University School of Medicine, Indianapolis, IN, USA.
Steven S AnIn Vivo Cellular and Molecular Imaging Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA; Physical Sciences in Oncology Center, Johns Hopkins University, Baltimore, MD, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
Phuoc T TranDepartment of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; In Vivo Cellular and Molecular Imaging Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Cellular and Molecular Medicine Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: tranp@jhmi.edu.
Johns Hopkins University · USSidney Kimmel Comprehensive Cancer Center · USIndiana University – Purdue University Indianapolis · USUniversity of Pittsburgh · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
Theranostic Imaging of Metastatic Prostate CancerP50CA103175 · NCI · JOHNS HOPKINS UNIVERSITY · PI BARKER, PETER B · 2003 to 2015
$17.9M
TRANS NETWORK PROJECTSU54CA143868 · NCI · JOHNS HOPKINS UNIVERSITY · PI WIRTZ, DENIS · 2009 to 2013
$13.7M
ONCOLOGY: CHEMOTHERAPY, IMMUNOLOGY, BIOLOGYT32CA009071 · NCI · JOHNS HOPKINS UNIVERSITY · PI Mary Y Armanios, Nilofer S. Azad · 1985 to 2026
$12.8M
Training Program in Cellular and Molecular MedicineT32GM008752 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI RAO, RAJINI · 2000 to 2019
$11.7M
Nrf2 as a critical determinant of smooth muscle functionR01HL107361 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI AN, STEVEN S · 2011 to 2015
$2.0M
Endocardial mechanisms of cardiac trabeculation and septationR01HL120920 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI FIRULLI, ANTHONY B. · 2014 to 2017
$1.8M
The role of Twist family bHLH factors in limb morphogenesisR01AR061392 · NIAMS · INDIANA UNIVERSITY INDIANAPOLIS · PI FIRULLI, ANTHONY B. · 2011 to 2015
$1.7M
Structure-Functions Studies of Twist1-induced Radioresistance in Lung CancerR01CA166348 · NCI · JOHNS HOPKINS UNIVERSITY · PI TRAN, PHUOC T. · 2013 to 2017
$1.7M
Cellular and Molecular Mechanisms of Left Ventricular Growth and MorphogenesisR01HL122123 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI FIRULLI, ANTHONY B. · 2014 to 2017
$1.6M
Laboratory Training Program in Radiation OncologyT32CA121937 · NCI · JOHNS HOPKINS UNIVERSITY · PI BUNZ, FRED · 2008 to 2012
$541k
Raman spectroscopy probes for assisting stereotactic breast biopsy needle placemeR43CA141868 · NCI · NEWTON LABORATORIES · PI FULGHUM, STEPHEN FREDERICK · 2009 to 2009
$100k
NCI NIH HHS P30 CA006973NCI NIH HHS P50 CA103175NCI NIH HHS P50CA103175NCI NIH HHS R01 CA166348NCI NIH HHS R01CA166348NCI NIH HHS R43 CA141868NCI NIH HHS T32 CA009071NCI NIH HHS T32 CA121937NCI NIH HHS T32CA121937NCI NIH HHS U54CA141868NCI NIH HHS U54 CA143868NHLBI NIH HHS HL107361NHLBI NIH HHS R01 HL107361NHLBI NIH HHS R01 HL120920NHLBI NIH HHS R01 HL122123NIAMS NIH HHS 1R0AR061392NIAMS NIH HHS R01 AR061392NIGMS NIH HHS T32 GM008752
6 · The paper itself

Abstract

The TWIST1 gene has diverse roles in development and pathologic diseases such as cancer. TWIST1 is a dimeric basic helix-loop-helix (bHLH) transcription factor existing as TWIST1-TWIST1 or TWIST1-E12/47. TWIST1 partner choice and DNA binding can be influenced during development by phosphorylation of Thr125 and Ser127 of the Thr-Gln-Ser (TQS) motif within the bHLH of TWIST1. The significance of these TWIST1 phosphorylation sites for metastasis is unknown. We created stable isogenic prostate cancer cell lines overexpressing TWIST1 wild-type, phospho-mutants, and tethered versions. We assessed these isogenic lines using assays that mimic stages of cancer metastasis. In vitro assays suggested the phospho-mimetic Twist1-DQD mutation could confer cellular properties associated with pro-metastatic behavior. The hypo-phosphorylation mimic Twist1-AQA mutation displayed reduced pro-metastatic activity compared to wild-type TWIST1 in vitro, suggesting that phosphorylation of the TWIST1 TQS motif was necessary for pro-metastatic functions. In vivo analysis demonstrates that the Twist1-AQA mutation exhibits reduced capacity to contribute to metastasis, whereas the expression of the Twist1-DQD mutation exhibits proficient metastatic potential. Tethered TWIST1-E12 heterodimers phenocopied the Twist1-DQD mutation for many in vitro assays, suggesting that TWIST1 phosphorylation may result in heterodimerization in prostate cancer cells. Lastly, the dual phosphatidylinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) inhibitor BEZ235 strongly attenuated TWIST1-induced migration that was dependent on the TQS motif. TWIST1 TQS phosphorylation state determines the intensity of TWIST1-induced pro-metastatic ability in prostate cancer cells, which may be partly explained mechanistically by TWIST1 dimeric partner choice.

Indexed as

Protein Interaction Domains and MotifsAmino Acid MotifsAnimalsBasic Helix-Loop-Helix ProteinsCell Line, TumorCell MovementCluster AnalysisDisease Models, AnimalEpithelial-Mesenchymal TransitionGene Expression ProfilingHeterograftsHumansMaleMutationNeoplasm MetastasisNuclear ProteinsBasic Helix-Loop-Helix ProteinsNuclear ProteinsPhosphatidylinositol 3-KinasesProtein Kinase InhibitorsProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesTWIST1 protein, humanTwist-Related Protein 1

Identifiers

PMID25622896
PMCPMC4309734
OpenAlexW2069989642

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.