Related Experiment Video

Updated: Feb 20, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

14.5K

TGF-β signalling and PEG10 are mutually exclusive and inhibitory in chondrosarcoma cells

Naohiro Shinohara1,2, Shingo Maeda3, Yuhei Yahiro1,2

  • 1Department of Medical Joint Materials, Kagoshima University, Kagoshima, Japan.

Scientific Reports
|October 19, 2017
PubMed

Insights

Distinguishing enchondroma from chondrosarcoma is challenging. This study identifies Paternally expressed gene 10 (PEG10) and SOX9 expression patterns, alongside transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) signaling, as key biomarkers for differentiating these cartilage tumors.

Area of Science:

  • Orthopedic oncology
  • Molecular pathology
  • Biomarker discovery

Background:

  • Histological differentiation between enchondroma and chondrosarcoma lacks definitive biomarkers, posing diagnostic challenges.
  • Transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) signaling pathways are implicated in cartilage tumor progression.
  • The role of Paternally expressed gene 10 (PEG10) in chondrosarcoma pathogenesis remains largely unexplored.

Purpose of the Study:

  • To identify novel molecular markers for distinguishing enchondroma from chondrosarcoma.
  • To investigate the interplay between TGF-β, BMP signaling, SOX9, and PEG10 in cartilage tumors.
  • To establish a potential diagnostic index for differentiating benign and malignant cartilage lesions.

Main Methods:

  • Immunohistochemistry was employed to assess phosphorylated SMAD3 and SMAD1/5 levels in enchondroma and chondrosarcoma samples.
  • Microarray analysis identified differentially expressed genes, including PEG10, between chondrosarcoma and normal chondrocyte cell lines.
  • In vitro experiments utilized TGF-β1 treatment, a TGF-β inhibitor (SB431542), and PEG10 knockdown in chondrosarcoma cells, coupled with reporter assays.

Main Results:

  • Chondrosarcomas exhibited heightened TGF-β and BMP signaling (pSMAD3, pSMAD1/5) compared to enchondromas, while SOX9 was downregulated in grade 1 chondrosarcoma.
  • PEG10 was overexpressed in chondrosarcoma cells relative to normal chondrocytes, but suppressed by TGF-β1 treatment, and showed stronger expression in enchondromas than chondrosarcomas.
  • PEG10 repressed TGF-β and BMP signaling pathways, and PEG10 knockdown increased pSMAD levels, indicating a mutual inhibitory relationship.

Conclusions:

  • Mutually exclusive expression of PEG10 and phosphorylated SMADs, along with differential SOX9 expression, serves as a potential index for distinguishing enchondroma from chondrosarcoma.
  • PEG10 and TGF-β signaling exhibit a reciprocal inhibitory interaction within chondrosarcoma cells.
  • These findings offer novel insights into the molecular mechanisms underlying cartilage tumor progression and provide potential diagnostic biomarkers.

More Related Videos

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling07:49

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling

Published on: August 3, 2018

11.8K
Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay11:38

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay

Published on: September 14, 2021

3.8K

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.7K
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...
7.4K
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
10.2K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.7K
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
18.7K
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
3.7K