Related Experiment Video

Updated: Jun 8, 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

USP7 deubiquitinates KRAS and promotes non-small cell lung cancer

Bin Huang1, Dan Cao1, Xiao Yuan2

  • 1State Key Laboratory of Chemical Oncogenomics, Laboratory of Structural Biology and Drug Discovery, Laboratory of Ubiquitination and Targeted Therapy, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, Guangdong 518055, China.

Cell Reports
|November 5, 2024
PubMed

Insights

Ubiquitin-specific protease 7 (USP7) deubiquitinates KRAS, enhancing non-small cell lung cancer (NSCLC) cell proliferation. Targeting USP7 offers a promising strategy against KRAS inhibitor resistance in NSCLC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • RAS oncogenic mutations drive tumorigenesis.
  • Ubiquitination regulates RAS protein function, but deubiquitination is less understood.
  • KRAS is a key oncogene in non-small cell lung cancer (NSCLC).

Purpose of the Study:

  • To investigate the role of deubiquitination in RAS regulation.
  • To identify deubiquitinating enzymes targeting KRAS.
  • To explore USP7 as a therapeutic target in NSCLC.

Main Methods:

  • Biochemical assays to study KRAS ubiquitination and deubiquitination.
  • Protein-protein interaction studies (USP7-KRAS binding).
  • Cell proliferation assays in NSCLC cell lines.
  • Analysis of patient tumor tissues for USP7 and KRAS correlation.

Main Results:

  • USP7 directly deubiquitinates KRAS at K147, removing K48-linked polyubiquitin chains.
  • USP7 stabilizes KRAS, promoting NSCLC cell proliferation.
  • High USP7 expression correlates with KRAS and poor survival in NSCLC patients.
  • USP7 inhibition suppresses NSCLC proliferation, overcoming resistance to KRAS-G12C inhibitors.

Conclusions:

  • USP7 is a key deubiquitinase regulating KRAS stability and function.
  • Targeting USP7 is a potential therapeutic strategy for NSCLC.
  • USP7 inhibition may overcome resistance to existing KRAS-targeted therapies.
Keywords:
AMG510CP: CancerKRASNSCLCRASUSP7cancerdeubiquitinationdrug resistanceinhibitorubiquitin

More Related Videos

The Soft Agar Colony Formation Assay08:01

The Soft Agar Colony Formation Assay

Published on: October 27, 2014

111.4K
Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma10:21

Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma

Published on: September 20, 2024

389

Related Concept Videos

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...
6.2K
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
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...
3.4K
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...
3.7K
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
3.9K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.2K