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Cited by 13Sarcoma Diagnosis and TreatmentChromatin Remodeling and CancerMuscle Physiology and Disorders

The c-Myc/AKT1/TBX3 Axis Is Important to Target in the Treatment of Embryonal Rhabdomyosarcoma

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Sims, Danica, Maranyane, Hapiloe Mabaruti, Damerell, Victoria, Govender, Dhirendra, Isaacs, Ashwin W., Peres, Jade, Prince, Sharon·2020·Cancers
DOI 10.3390/cancers12020501PMC PMC7072582
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Abstract

Rhabdomyosarcoma is a highly aggressive malignant cancer that arises from skeletal muscle progenitor cells and is the third most common solid tumour in children. Despite significant advances, rhabdomyosarcoma still presents a therapeutic challenge, and while targeted therapy has shown promise, there are limited options because the molecular drivers of rhabdomyosarcoma are poorly understood. We previously reported that the T-box transcription factor 3 (TBX3), which has been identified as a druggable target in many cancers, is overexpressed in rhabdomyosarcoma patient samples and cell lines. To identify new molecular therapeutic targets to treat rhabdomyosarcoma, this study investigates the potential oncogenic role(s) for TBX3 and the factors responsible for upregulating it in this cancer. To this end, rhabdomyosarcoma cell culture models in which TBX3 was either stably knocked down or overexpressed were established and the impact on key hallmarks of cancer were examined using growth curves, soft agar and scratch motility assays, as well as tumour-forming ability in nude mice. Our data show that TBX3 promotes substrate-dependent and -independent proliferation, migration and tumour formation. We further reveal that TBX3 is upregulated by c-Myc transcriptionally and AKT1 post-translationally. This study identifies c-Myc/AKT1/TBX3 as an important axis that could be targeted for the treatment of rhabdomyosarcoma.

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Authors
Sims, D., Maranyane, H. M., Damerell, V., Govender, D., Isaacs, A. W., Peres, J., & Prince, S.
Affiliations
University of Cape Town (ZA)
Corresponding author
Prince, Sharon
ORCID
Venue
Cancers
Publisher
MDPI AG
Published
2020-02-21
Volume
12
Issue
2
Pages
501
ISSN
2072-6694 (ISSN-L)
DOI
10.3390/cancers12020501
PMC
PMC7072582
OpenAlex
W3007401772
Cited by
13
References
98
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1.13
Type
journal article
Language
en
Open access
Licence
Locations
  • Cancers (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Cancer Association of South Africa (04/01/17-04/01/20)
  • South African Medical Research Council (05/01/16-05/01/18)
  • National Research Foundation Singapore (105255)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Keywords
embryonal rhabdomyosarcoma, TBX3, c-Myc, AKT1, transcriptional regulation, post-translational regulation, cell proliferation, cell migration, tumor formation, therapeutic target

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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