Related Experiment Video

Updated: Jun 21, 2025

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

17.9K

Anlotinib destabilizes PAX3-FOXO1 to induce rhabdomyosarcoma cell death via upregulating NEK2

Zian Song1, Baocheng Gong1, Tongyuan Qu1

  • 1Department of Pediatric Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Centre for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|July 12, 2024
PubMed
Abstract

Insights

Anlotinib effectively treats rhabdomyosarcoma (RMS) by degrading the PAX3-FOXO1 fusion protein. This targeted approach shows promise for improving outcomes in pediatric cancer patients with this aggressive subtype.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Rhabdomyosarcoma (RMS) is a common pediatric soft tissue sarcoma.
  • PAX3-FOXO1 fusion gene positivity indicates a poor prognosis in RMS.
  • No targeted therapies currently exist for PAX3-FOXO1-positive RMS.

Purpose of the Study:

  • To investigate the efficacy of anlotinib against RMS.
  • To explore the role of PAX3-FOXO1 in anlotinib's therapeutic effects.
  • To elucidate the mechanism of anlotinib action in RMS.

Main Methods:

  • Cell viability, apoptosis, cell cycle, invasion, and migration assays were performed.
  • Western blotting, qPCR, and xenograft experiments assessed anlotinib's effects.
  • RNA-seq and co-immunoprecipitation identified the regulatory mechanism of anlotinib on PAX3-FOXO1.

Main Results:

  • Anlotinib inhibited RMS cell proliferation, induced apoptosis, and caused G2/M phase arrest.
  • Anlotinib impeded tumor growth in vivo and its efficacy was enhanced by PAX3-FOXO1 downregulation.
  • Anlotinib upregulated NEK2, promoting PAX3-FOXO1 degradation via the ubiquitin-proteasome pathway.

Conclusions:

  • Anlotinib effectively inhibits RMS progression and promotes PAX3-FOXO1 degradation.
  • Anlotinib represents a potential targeted therapy for PAX3-FOXO1-positive RMS.
Keywords:
AnlotinibPAX3-FOXO1RhabdomyosarcomaUbiquitination

More Related Videos

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

6.9K
Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:39

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

73

Related Concept Videos

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
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
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
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.5K