Related Experiment Video

Updated: Feb 4, 2026

Acute Kidney Injury Model Induced by Cisplatin in Adult Zebrafish
13:25

Acute Kidney Injury Model Induced by Cisplatin in Adult Zebrafish

Published on: May 15, 2021

6.6K

FBXW7 modulates malignant potential and cisplatin-induced apoptosis in cholangiocarcinoma through NOTCH1 and MCL1

Akiko Mori1, Kunihiro Masuda1, Hideo Ohtsuka1

  • 1Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.

Cancer Science
|October 11, 2018
PubMed

Insights

The tumor suppressor FBXW7 (F-box and WD repeat domain-containing 7) is crucial in cholangiocarcinoma. Lower FBXW7 levels correlate with worse patient survival and increased cancer cell migration and drug resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • The ubiquitin ligase FBXW7 (F-box and WD repeat domain-containing 7) acts as a tumor suppressor by degrading oncoproteins.
  • FBXW7 inhibition generally enhances cancer malignancy.
  • The role of FBXW7 in cholangiocarcinoma (bile duct cancer) remains largely unexplored.

Purpose of the Study:

  • To investigate the prognostic significance of FBXW7 in cholangiocarcinoma.
  • To elucidate the mechanisms by which FBXW7 influences cholangiocarcinoma progression, focusing on its substrates NOTCH1 and MCL1.

Main Methods:

  • Analysis of FBXW7 expression in cholangiocarcinoma patient samples.
  • Correlation of FBXW7 levels with clinicopathological features and patient survival.
  • Investigation of FBXW7's role in regulating NOTCH1 and MCL1 stability and function.
  • Assessment of cholangiocarcinoma cell migration, self-renewal, and apoptosis sensitivity following FBXW7 manipulation.

Main Results:

  • FBXW7 expression inversely correlated with poor disease-free and overall survival in cholangiocarcinoma patients.
  • FBXW7 was identified as an independent prognostic factor for survival.
  • FBXW7 depletion led to NOTCH1 accumulation, promoting cholangiocarcinoma cell migration and self-renewal.
  • FBXW7 suppression induced MCL1 upregulation, conferring resistance to cisplatin-induced apoptosis in a context-dependent manner.

Conclusions:

  • FBXW7 functions as a tumor suppressor in cholangiocarcinoma.
  • FBXW7 modulates cholangiocarcinoma malignancy through the independent regulation of NOTCH1 and MCL1.
  • Targeting FBXW7 or its downstream pathways may offer therapeutic strategies for cholangiocarcinoma.
Keywords:
FBXW7 proteinNOTCH1 proteincholangiocarcinomacisplatinmyeloid cell leukemia sequence 1 protein

More Related Videos

Detection of Mitochondria Membrane Potential to Study CLIC4 Knockdown-induced HN4 Cell Apoptosis In Vitro13:20

Detection of Mitochondria Membrane Potential to Study CLIC4 Knockdown-induced HN4 Cell Apoptosis In Vitro

Published on: July 17, 2018

10.8K
Robotic Taj Mahal Hepatectomy for Hilar Cholangiocarcinoma09:19

Robotic Taj Mahal Hepatectomy for Hilar Cholangiocarcinoma

Published on: July 14, 2022

4.3K

Related Concept Videos

Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
14.5K
Potential Energy00:52

Potential Energy

The energy stored by a structure and location of matter in space is called potential energy. For instance, raising a kettlebell changes its spatial location and increases its potential energy. Similarly, a stretched rubber band contains potential energy which, under certain conditions, can be converted into other forms of energy, such as kinetic energy.
Chemical bonds that form attractive forces between atoms also contain potential energy, called chemical energy. When a chemical reaction...
42.7K
Potential Energy01:09

Potential Energy

A conservative force, such as a gravitational or elastic force, gives the body the capacity to do work. This capacity, measured as the potential energy, depends on the body's location or “position” relative to a fixed reference position or datum. The gravitational potential energy is considered zero at the reference point. Suppose a body is located at some vertical distance above a fixed horizontal reference or datum. In that case, the weight of the body has positive gravitational potential...
1.0K
Standard Electrode Potentials03:02

Standard Electrode Potentials

On comparing the reactivity of silver and lead, it is observed that the two ionic species, Ag+ (aq) and Pb2+ (aq), show a difference in their redox reactivity towards copper: the silver ion undergoes spontaneous reduction, while the lead ion does not. This relative redox activity can be easily quantified in electrochemical cells by a property called cell potential. This property is commonly known as cell voltage in electrochemistry, and it is a measure of the energy which accompanies the charge...
50.3K
Cell Potential and Free Energy02:58

Cell Potential and Free Energy

Thermodynamics of a Redox Reaction
Thermodynamics is the branch of physics dealing with the relationship between heat and other forms of energy. In an electrochemical cell, chemical energy is converted into electrical energy.
Thus, a link can be predicted between cell potential, free energy change, and the equilibrium constant for the reaction. Cell potential can also be measured as the oxidant or the reducing strength, and similar acid-base strength measures are reflected in equilibrium...
46.5K
The Resting Membrane Potential01:21

The Resting Membrane Potential

Overview
142.6K