Related Experiment Video

Updated: Jan 28, 2026

De Novo Generation of Somatic Stem Cells by YAP/TAZ
13:05

De Novo Generation of Somatic Stem Cells by YAP/TAZ

Published on: May 7, 2018

9.6K

MEK nuclear localization promotes YAP stability via sequestering β-TrCP in KRAS mutant cancer cells

Huanji Xu1, Sheng Zhou1, Hongwei Xia1

  • 1Department of Abdominal Oncology, Cancer Center and Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, China.

Cell Death and Differentiation
|March 6, 2019
PubMed

Insights

KRAS-targeted drugs face resistance from tumors. Inhibiting KRAS promotes MEK nuclear localization, stabilizing YAP and aiding tumor survival. Targeting MEK nuclear localization offers new colon cancer treatment strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Tumors develop resistance to KRAS-targeted therapies, limiting treatment efficacy.
  • Understanding resistance mechanisms is crucial for developing effective KRAS-mutant cancer treatments.

Purpose of the Study:

  • To elucidate the role of MEK nuclear localization in resistance to KRAS ablation.
  • To investigate the relationship between MEK nuclear localization, YAP stabilization, and tumor malignancy.
  • To explore novel therapeutic strategies targeting MEK nuclear localization in KRAS-mutant colon cancer.

Main Methods:

  • Analysis of tissue microarrays from colon tumors.
  • In vitro and in vivo experiments involving KRAS knockdown, MEK inhibition (trametinib), and deltarasin treatment.
  • Investigation of protein interactions including MEK, YAP, and β-TrCP.

Main Results:

  • Inhibition of mutant KRAS promotes MEK nuclear localization, contributing to drug resistance.
  • Aberrant MEK nuclear localization correlates with YAP levels and colon tumor malignancy.
  • Trametinib prevents MEK nuclear localization, leading to YAP degradation and synergistic tumor suppression when combined with KRAS knockdown or deltarasin.

Conclusions:

  • MEK nuclear localization is an alternative resistance mechanism to KRAS-targeted drugs.
  • Targeting MEK nuclear localization by trametinib offers a promising strategy for overcoming resistance in KRAS-mutant colon cancers.
  • Combined inhibition of MEK nuclear localization and KRAS signaling synergistically reduces cancer cell viability.

More Related Videos

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

14.3K
Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

6.5K

Related Concept Videos

Nuclear Stability03:18

Nuclear Stability

Protons and neutrons, collectively called nucleons, are packed together tightly in a nucleus. With a radius of about 10−15 meters, a nucleus is quite small compared to the radius of the entire atom, which is about 10−10 meters. Nuclei are extremely dense compared to bulk matter, averaging 1.8 × 1014 grams per cubic centimeter. If the earth’s density were equal to the average nuclear density, the earth’s radius would be only about 200 meters.
To hold positively charged protons together...
23.2K
Nuclear Localization Signals and Import01:46

Nuclear Localization Signals and Import

Proteins targeted to the nucleus carry short stretches of amino acid sequences called the nuclear localization signal or NLS. Classical nuclear localization signals are of two types: monopartite and bipartite NLS. Monopartite classical NLS (cNLS) consists of a single cluster of 4-8 amino acids. Bipartite cNLS consists of two clusters of  2-3 amino acids and a 9-12 residue long proline-rich linker bridging the two clusters. Signal clusters are rich in positively charged amino acids such as...
7.7K
The Eukaryotic Promoter Region02:40

The Eukaryotic Promoter Region

The eukaryotic promoter region is a segment of DNA located upstream of a gene. It contains an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences.  The proximal promoter region is located in the vicinity of the gene and has cis-regulatory sequences and the core promoter. The core promoter is the binding site for RNA polymerase and is usually located between -35 and +35 nucleotides from the transcription start site. The distal promoter regions are...
18.7K
Nuclear Binding Energy02:13

Nuclear Binding Energy

The difference between the calculated and experimentally measured masses is known as the mass defect of the atom. In the case of helium-4, the mass defect indicates a “loss” in mass of 4.0331 amu – 4.0026 amu = 0.0305 amu. The loss in mass accompanying the formation of an atom from protons, neutrons, and electrons is due to the conversion of that mass into energy that is evolved as the atom forms. The nuclear binding energy is the energy produced when the atoms’ nucleons are bound...
14.7K
Non-nuclear Inheritance01:29

Non-nuclear Inheritance

Most DNA resides in the nucleus of a cell. However, some organelles in the cell cytoplasm⁠—such as chloroplasts and mitochondria⁠—also have their own DNA. These organelles replicate their DNA independently of the nuclear DNA of the cell in which they reside. Non-nuclear inheritance describes the inheritance of genes from structures other than the nucleus.
23.1K
Nuclear Fusion02:45

Nuclear Fusion

The process of converting very light nuclei into heavier nuclei is also accompanied by the conversion of mass into large amounts of energy, a process called fusion. The principal source of energy in the sun is a net fusion reaction in which four hydrogen nuclei fuse and ultimately produce one helium nucleus and two positrons.
A helium nucleus has a mass that is 0.7% less than that of four hydrogen nuclei; this lost mass is converted into energy during the fusion. This reaction produces about...
33.8K