Related Experiment Video

Updated: Jun 6, 2026

A Preclinical Mouse Model of Osteosarcoma to Define the Extracellular Vesicle-mediated Communication Between Tumor and Mesenchymal Stem Cells
11:15

A Preclinical Mouse Model of Osteosarcoma to Define the Extracellular Vesicle-mediated Communication Between Tumor and Mesenchymal Stem Cells

Published on: May 6, 2018

FTO-mediated m6A modification of protein disulfide-isomerase activates VEGFA-VEGFR2 to suppress programmed cell death

Jiashi Wang1, Yingying Hao2, Ming He1

  • 1Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, PR China.

The Journal of Pathology
|June 5, 2026
PubMed

Insights

Protein disulfide-isomerase (PDI) promotes osteosarcoma (OS) growth by upregulating VEGFA-VEGFR2 signaling. Targeting PDI or its regulator FTO may inhibit OS progression and metastasis, offering new therapeutic strategies for this bone cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Osteosarcoma (OS) is a primary bone cancer.
  • Inducing programmed cell death (PCD) can hinder OS progression.
  • The role of Protein disulfide-isomerase (PDI) in OS cell death is unclear.

Purpose of the Study:

  • To investigate the functional role of PDI (encoded by P4HB) in osteosarcoma progression.
  • To elucidate the upstream and downstream mechanisms regulating PDI in OS.
  • To explore PDI's impact on various programmed cell death pathways in OS.

Main Methods:

  • Assessed P4HB expression in OS tissues and cell lines via RT-qPCR.
  • Evaluated P4HB effects on OS cell lines, including migration and invasiveness.
  • Utilized Western blotting to assess PDI's impact on apoptosis, ferroptosis, and pyroptosis.
  • Performed bioinformatics analysis and xenograft studies to identify regulatory mechanisms.

Main Results:

  • Elevated P4HB expression was found in OS tissues and cells.
  • Downregulating P4HB suppressed OS cell growth, migration, invasiveness, and induced PCD.
  • PDI was found to upregulate VEGFA-VEGFR2 signaling.
  • The m6A demethylase FTO reduced P4HB m6A levels, enhancing VEGFA-VEGFR2 signaling and OS cell proliferation, migration, and invasion while decreasing PCD.
  • FTO knockdown inhibited OS tumor growth and lung metastasis.

Conclusions:

  • PDI (P4HB) promotes osteosarcoma progression by activating the VEGFA-VEGFR2 signaling axis.
  • FTO-mediated m6A modification of P4HB is a key mechanism regulating PCD in OS.
  • Targeting the PDI/VEGFA-VEGFR2 axis or FTO presents a potential therapeutic strategy for osteosarcoma.
Keywords:
fat mass and obesity‐associated proteinm6A modificationosteosarcomaprogrammed cell deathprotein disulfide‐isomerasevascular endothelial growth factor A ‐ vascular endothelial growth factor receptor 2 signaling

More Related Videos

Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models04:25

Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models

Published on: October 28, 2021

A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate07:31

A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate

Published on: May 3, 2021

Related Concept Videos

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 hydroxylase and factor...
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 are of three kinds RI, RII, and RIII. The RI...
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...
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...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...