1. The c-Myc/AKT1/TBX3 axis is important to target in the treatment of embryonal rhabdomyosarcoma
- Author
-
Victoria Damerell, Danica Sims, Jade Peres, Sharon Prince, Ashwin W Isaacs, Dhirendra Govender, and Hapiloe Mabaruti Maranyane
- Subjects
0301 basic medicine ,Cancer Research ,medicine.medical_treatment ,AKT1 ,Biology ,lcsh:RC254-282 ,Article ,Targeted therapy ,embryonal rhabdomyosarcoma (ERMS) ,03 medical and health sciences ,0302 clinical medicine ,oncogene ,medicine ,T-box transcription factor-3 (TBX3) ,childhood cancer ,Progenitor cell ,Rhabdomyosarcoma ,Transcription factor ,neoplasms ,Oncogene ,Cancer ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,030104 developmental biology ,c-Myc ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Embryonal rhabdomyosarcoma ,rhabdomyosarcoma (RMS) - 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.
- Published
- 2023