Related Experiment Video

Updated: Aug 14, 2025

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
09:29

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies

Published on: September 30, 2016

13.8K

Targeting KRAS-mutant stomach/colorectal tumors by disrupting the ERK2-p53 complex

Xiang Wang1, Qing Xie1, Yan Ji2

  • 1The CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China.

Cell Reports
|January 15, 2023
PubMed

Insights

Targeting the ERK2-p53 complex with MEK/ERK inhibitors halts KRAS-mutant cancer growth. This approach disrupts a key complex, promoting p53 activation and tumor cell death in a p53-dependent manner.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • KRAS mutations drive cancer proliferation and metastasis, necessitating targeted therapies.
  • The ERK2-p53 complex is a novel target identified in KRAS-mutant cancers.

Purpose of the Study:

  • To investigate the role of the ERK2-p53 complex in KRAS-mutant cancers.
  • To evaluate MEK1/2 and ERK2 inhibitors as a therapeutic strategy for KRAS-mutant tumors.

Main Methods:

  • Observation of ERK2-p53 complex formation in cancer cells.
  • Application of MEK1/2 and ERK2 inhibitors (e.g., trametinib).
  • Genome-wide knockout screening and p53-dependent apoptosis assays.

Main Results:

  • Mutant KRAS promotes ERK2-p53 complex formation, suppressing p53 activation.
  • MEK1/2 and ERK2 inhibitors disrupt the complex by reducing ERK2 phosphorylation.
  • Disruption leads to p53 acetylation, PUMA transcription, and apoptosis in KRAS-mutant tumors.

Conclusions:

  • The ERK2-p53 complex is a critical mediator in KRAS-driven tumorigenesis.
  • Targeting this complex with inhibitors offers a promising therapeutic strategy for KRAS-mutant cancers.
Keywords:
CP: CancerERK2KRASp53stomach/colorectal cancertrametinib

More Related Videos

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer06:51

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

18.0K
Reliably Engineering and Controlling Stable Optogenetic Gene Circuits in Mammalian Cells09:20

Reliably Engineering and Controlling Stable Optogenetic Gene Circuits in Mammalian Cells

Published on: July 6, 2021

2.5K

Related Concept Videos

Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.6K
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...
7.8K
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
6.4K
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...
4.6K
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