Related Experiment Video

Updated: Aug 5, 2025

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
11:27

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α

Published on: November 2, 2018

9.2K

Non-Oncogene Addiction of KRAS-Mutant Cancers to IL-1β via Versican and Mononuclear IKKβ

Magda Spella1,2, Giannoula Ntaliarda1,2, Georgios Skiadas1,2

  • 1Department of Physiology, Faculty of Medicine, University of Patras, 26504 Rio, Greece.

Cancers
|March 29, 2023
PubMed

Insights

KRAS-mutant cancers rely on IL-1β signaling driven by versican and IKKβ. Inhibiting these targets halts metastasis, offering new therapeutic strategies for these aggressive cancers.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • KRAS-mutant cancers are a significant unmet medical need due to their metastatic and lethal nature.
  • Targeting inflammation, specifically interleukin-1 beta (IL-1β) and nuclear factor-kappa B (NF-κB), shows promise but requires specific approaches.

Purpose of the Study:

  • To elucidate the mechanism of IL-1β addiction in KRAS-mutant cancers.
  • To identify key molecular players in KRAS-mutant cancer metastasis.
  • To explore potential therapeutic targets for KRAS-mutant cancers.

Main Methods:

  • Human pan-cancer analysis and experimental models.
  • NF-κB reporter assays, transcriptome, and proteome profiling.
  • Versican silencing and IKKβ deletion in macrophages.

Main Results:

  • KRAS-mutant tumors utilize inflammatory versican signaling to activate macrophage IKKβ, leading to IL-1β release.
  • Tumor-specific versican silencing and macrophage IKKβ deletion suppressed myeloid NF-κB activation and metastasis.
  • Versican and IKKβ are overexpressed and mutually dependent in human cancers, showing diagnostic and prognostic value.

Conclusions:

  • KRAS-mutant cancers exhibit a non-oncogene addiction to IL-1β, mediated by versican and IKKβ.
  • Versican and IKKβ are critical drivers of metastasis in KRAS-mutant cancers.
  • Targeting IL-1β, versican, and IKKβ presents a promising therapeutic strategy for KRAS-mutant cancers.
Keywords:
bioluminescencecancerinflammationinterleukin-1βnon-oncogene addictionnuclear factor-κB

More Related Videos

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

6.1K
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

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...
6.3K
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
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...
9.1K
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...
7.7K
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
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:
4.0K