Related Experiment Video

Updated: Apr 23, 2026

The Murine Choline-Deficient, Ethionine-Supplemented CDE Diet Model of Chronic Liver Injury
07:27

The Murine Choline-Deficient, Ethionine-Supplemented CDE Diet Model of Chronic Liver Injury

Published on: October 21, 2017

11.2K

Neddylation pathway is up-regulated in human intrahepatic cholangiocarcinoma and serves as a potential therapeutic

Qiang Gao1, Guang-Yang Yu2, Jie-Yi Shi1

  • 1Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, P. R. China. Contributed equally to this work.

Oncotarget
|September 18, 2014
PubMed

Insights

Targeting the neddylation pathway shows promise for intrahepatic cholangiocarcinoma (ICC) treatment. Upregulated neddylation markers predict recurrence, and an inhibitor, MLN4924, reduced ICC cell viability and tumor growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The neddylation pathway is crucial for protein modification and cellular processes.
  • Aberrant neddylation has been implicated in various cancers, including intrahepatic cholangiocarcinoma (ICC).
  • Targeting the neddylation pathway presents a novel therapeutic strategy for cancer treatment.

Purpose of the Study:

  • To investigate the clinical relevance of neddylation pathway components in ICC.
  • To evaluate the therapeutic potential of inhibiting the neddylation pathway in ICC.
  • To explore the efficacy of MLN4924, a NEDD8-activating enzyme inhibitor, in ICC models.

Main Methods:

  • Immunohistochemistry was performed on 322 ICC patient samples to assess neddylation markers.
  • In vitro studies utilized ICC cell lines treated with MLN4924 and cisplatin.
  • In vivo efficacy was evaluated using a cholangiocarcinoma xenograft mouse model.

Main Results:

  • Upregulation of E1 (NAE1, UBA3), E2 (UBC12) enzymes, and global NEDD8 conjugation was observed in over two-thirds of ICC cases.
  • NAE1 expression independently predicted postoperative recurrence, and combined NEDD8/NAE1 levels improved outcome prediction.
  • MLN4924 reduced ICC cell viability, potentiated cisplatin's effect, inhibited tumor growth, and induced cell cycle arrest, senescence, or apoptosis by inactivating Cullin-Ring ligase (CRL).

Conclusions:

  • The neddylation pathway is significantly upregulated and involved in ICC progression.
  • Targeting the neddylation pathway, specifically with MLN4924, offers a promising therapeutic strategy for ICC.
  • Combined NEDD8/NAE1 expression serves as a potential prognostic biomarker for ICC patients.

More Related Videos

Advances in Human Induced Pluripotent Stem Cell-Derived Chimeric Antigen Receptor-Expressing Natural Killer Cells11:08

Advances in Human Induced Pluripotent Stem Cell-Derived Chimeric Antigen Receptor-Expressing Natural Killer Cells

Published on: February 14, 2025

1.9K
An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis06:38

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis

Published on: September 12, 2019

8.5K

Related Concept Videos

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...
7.4K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.0K
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...
6.1K
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...
4.0K
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...
4.6K