Related Experiment Video

Updated: Nov 7, 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

18.2K

TRIM25 activates AKT/mTOR by inhibiting PTEN via K63-linked polyubiquitination in non-small cell lung cancer

Yuan-Ming He1,2, Xiu-Min Zhou3, Shuo-Yi Jiang1,2

  • 1Guangdong Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.

Acta Pharmacologica Sinica
|May 1, 2021
PubMed

Insights

The ubiquitin ligase TRIM25 promotes non-small cell lung cancer (NSCLC) by inhibiting PTEN. The antibacterial nitroxoline reactivates PTEN, offering a potential therapeutic strategy for NSCLC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The PTEN/AKT/mTOR pathway is crucial in cell signaling and frequently dysregulated in non-small cell lung cancer (NSCLC).
  • Understanding the regulatory mechanisms of this pathway in NSCLC is essential for developing effective treatments.

Purpose of the Study:

  • To investigate the role of the ubiquitin ligase TRIM25 in NSCLC pathogenesis.
  • To elucidate the molecular mechanisms by which TRIM25 affects the PTEN/AKT/mTOR pathway.
  • To explore potential therapeutic interventions targeting TRIM25 or its associated pathways.

Main Methods:

  • Analysis of TRIM25 expression in NSCLC tissues.
  • In vitro studies to assess TRIM25's effect on NSCLC cell survival and tumor growth.
  • Biochemical assays to determine TRIM25's interaction with PTEN and its ubiquitination status.
  • Investigation of nitroxoline's effect on PTEN activity and NSCLC apoptosis.

Main Results:

  • TRIM25 is highly expressed in NSCLC and promotes tumor progression.
  • TRIM25 binds to PTEN, mediating K63-linked ubiquitination at K266, which inhibits PTEN translocation and activity.
  • This leads to PI(3,4,5)P3 accumulation and activation of the AKT/mTOR signaling pathway.
  • Nitroxoline reduces PTEN ubiquitination, enhances PTEN activity, and sensitizes NSCLC cells to cisplatin-induced apoptosis.

Conclusions:

  • TRIM25 plays a significant role in NSCLC by negatively regulating PTEN.
  • Targeting TRIM25 or modulating PTEN activity with agents like nitroxoline presents a promising therapeutic avenue for NSCLC treatment.
Keywords:
K63-linked polyubiquitinationPTENTRIM25non-small cell lung cancer

More Related Videos

Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies07:47

Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies

Published on: September 15, 2023

1.9K
Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

413

Related Concept Videos

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...
4.4K
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...
4.0K
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...
4.8K
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...
6.8K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
9.9K
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...
6.9K