Related Experiment Video

Updated: Aug 9, 2025

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
04:01

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics

Published on: March 15, 2024

1.1K

FANCD2 inhibits ferroptosis by regulating the JAK2/STAT3 pathway in osteosarcoma

Xujun Li1, Jiangyi Liu2

  • 1Department of Orthopaedic, Minhang Hospital, Fudan University, No.170, Xinsong Road, Xinzhuang Town, Minhang District, Shanghai City, 201199, China.

BMC Cancer
|February 23, 2023
PubMed
Abstract

Insights

Fanconi anemia complementation group D2 (FANCD2) promotes osteosarcoma progression. Silencing FANCD2 induces ferroptosis and inhibits tumor growth by regulating the JAK2/STAT3 pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Death Mechanisms

Background:

  • Osteosarcoma progression is a complex process involving multiple molecular pathways.
  • Fanconi anemia complementation group D2 (FANCD2) is implicated in DNA repair and genomic stability.
  • The role of FANCD2 in regulating ferroptosis during osteosarcoma development requires further investigation.

Purpose of the Study:

  • To elucidate the function of FANCD2 in regulating ferroptosis in osteosarcoma.
  • To explore the impact of FANCD2 on osteosarcoma cell viability, invasion, migration, and tumor growth.
  • To investigate the underlying molecular mechanisms, including the JAK2/STAT3 axis.

Main Methods:

  • Western blot analysis to assess FANCD2 and pathway-related gene expression.
  • Assessment of ferroptosis markers: lipid peroxidation, labile iron pool (LIP), and ferrous iron (Fe2+).
  • Functional assays including cell viability, invasion, and migration assays; in vivo tumor growth studies.

Main Results:

  • FANCD2 expression was elevated in osteosarcoma cells.
  • FANCD2 knockdown significantly reduced cell viability, invasion, migration, and tumor growth.
  • FANCD2 silencing increased ferroptosis markers (LIP, Fe2+, lipid peroxidation), effects reversed by Fer-1.
  • FANCD2 knockdown decreased JAK2 and STAT3 expression; STAT3 activation reversed the tumor-suppressive effects.

Conclusions:

  • FANCD2 silencing suppresses osteosarcoma progression by inducing ferroptosis.
  • The JAK2/STAT3 signaling pathway is a key mediator of FANCD2's role in osteosarcoma.
  • Targeting FANCD2 and the JAK2/STAT3 axis offers potential therapeutic strategies for osteosarcoma.
Keywords:
FANCD2FerroptosisJAK2/STAT3 pathwayOsteosarcoma

More Related Videos

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

8.3K
Stimulation of Notch Signaling in Mouse Osteoclast Precursors08:01

Stimulation of Notch Signaling in Mouse Osteoclast Precursors

Published on: February 28, 2017

7.9K

Related Concept Videos

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
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
9.1K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.9K
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...
3.8K
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...
7.5K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.8K