Related Experiment Video

Updated: Jun 23, 2025

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
09:37

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells

Published on: August 25, 2021

1.8K

Myc upregulates Ggct, γ-glutamylcyclotransferase to promote development of p53-deficient osteosarcoma

Tomoya Ueno1, Shohei Otani1, Yuki Date1

  • 1Department of Molecular Tumor Biology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.

Cancer Science
|June 26, 2024
PubMed

Insights

This study reveals that γ-glutamylcyclotransferase (Ggct) is upregulated by Myc in osteosarcoma (OS). Targeting Ggct may offer a new strategy for treating this bone cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Osteosarcoma (OS) development in humans involves TP53 gene alterations.
  • In mice, c-Myc (Myc) oncogenicity is essential for OS development following p53 loss.
  • The specific genes targeted by Myc in OS tumorigenesis remain largely uncharacterized.

Purpose of the Study:

  • To investigate the role of γ-glutamylcyclotransferase (Ggct) in human and mouse OS.
  • To elucidate the regulatory mechanism of Ggct by Myc in OS.
  • To assess the therapeutic potential of targeting Ggct in OS.

Main Methods:

  • Analysis of GGCT as a prognostic factor in human OS.
  • Assessment of Ggct deletion effects on p53-deficient osteosarcomagenesis in mice.
  • Investigation of Myc binding to the Ggct promoter using genome editing techniques.

Main Results:

  • GGCT expression is a significant poor prognostic factor for human OS.
  • Deletion of Ggct significantly suppresses osteosarcomagenesis in p53-deficient mice.
  • Myc directly upregulates Ggct by binding to its promoter; disrupting this site reduces OS cell tumorigenicity.

Conclusions:

  • GGCT is a Myc-driven oncogene in osteosarcoma.
  • GGCT is frequently upregulated in cancer cells, making it a promising therapeutic target.
  • Targeting GGCT presents a potential new avenue for osteosarcoma treatment.
Keywords:
GgctMycglutathioneosteosarcomap53

More Related Videos

Yeast As a Chassis for Developing Functional Assays to Study Human P5314:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

9.5K
Author Spotlight: Genetically Engineered Mouse Models and Pathological Characterization of Neurofibromatosis Type 1 Associated Tumors08:57

Author Spotlight: Genetically Engineered Mouse Models and Pathological Characterization of Neurofibromatosis Type 1 Associated Tumors

Published on: May 17, 2024

1.9K

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
4.0K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.5K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.4K