ArticleScientific reports2015
mTORC1 maintains the tumorigenicity of SSEA-4(+) high-grade osteosarcoma.
Article in Scientific reports, 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 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
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- Ganglioside SSEA-4 in Ewing sarcoma marks a tumor cell population with aggressive features and is a potential cell-surface immune target.Scientific reports · 2024Article
- Mechanism of Antigen Presentation and Specificity of Antibody Cross-Reactivity Elicited by an Oligosaccharide-Conjugate Cancer Vaccine.Journal of the American Chemical Society · 2023Article
- Combined Effect of Anti-SSEA4 and Anti-Globo H Antibodies on Breast Cancer Cells.ACS chemical biology · 2021Article
- Modeling the Tumor Microenvironment and Pathogenic Signaling in Bone Sarcoma.Tissue engineering. Part B, Reviews · 2020Review
- Understanding and Modeling Metastasis Biology to Improve Therapeutic Strategies for Combating Osteosarcoma Progression.Frontiers in oncology · 2020Review
- Mechanically tunable coaxial electrospun models of YAP/TAZ mechanoresponse and IGF-1R activation in osteosarcoma.Acta biomaterialia · 2019Article
- Stage-specific embryonic antigen-4 is a histological marker reflecting the malignant behavior of prostate cancer.Glycoconjugate journal · 2019Article
- Role of mTORC1 in intestinal epithelial repair and tumorigenesis.Cellular and molecular life sciences : CMLS · 2019Review
- Carbohydrate Targets for CAR T Cells in Solid Childhood Cancers.Frontiers in oncology · 2018Review
- Thrombospondin-1 promotes cell migration, invasion and lung metastasis of osteosarcoma through FAK dependent pathway.Oncotarget · 2017Article
- Antitumor effect of focal adhesion kinase inhibitor PF562271 against human osteosarcoma in vitro and in vivo.Cancer science · 2017Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inactivation of p53 and/or Rb pathways restrains osteoblasts from cell-cycle exit and terminal differentiation, which underpins osteosarcoma formation coupled with dedifferentiation. Recently, the level of p-S6K was shown to independently predict the prognosis for osteosarcomas, while the reason behind this is not understood. Here we show that in certain high-grade osteosarcomas, immature SSEA-4(+) tumor cells represent a subset of tumor-initiating cells (TICs) whose pool size is maintained by mTORC1 activity. mTORC1 supports not only SSEA-4(+) cell self-renewal through S6K but also the regeneration of SSEA-4(+) TICs by SSEA-4(-) osteosarcoma cell dedifferentiation. Mechanistically, active mTORC1 is required to prevent a likely upregulation of the cell-cycle inhibitor p27 independently of p53 or Rb activation, which otherwise effectively drives the terminal differentiation of SSEA-4(-) osteosarcoma cells at the expense of dedifferentiation. Thus, mTORC1 is shown to critically regulate the retention of tumorigenicity versus differentiation in discrete differentiation phases in SSEA-4(+) TICs and their progeny.
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