Related Experiment Video

Updated: May 22, 2026

Real-Time Quantitative Measurement of Tumor Cell Migration and Invasion Following Synthetic mRNA Transfection
11:00

Real-Time Quantitative Measurement of Tumor Cell Migration and Invasion Following Synthetic mRNA Transfection

Published on: June 23, 2023

Oncogenic Kras expression in postmitotic neurons leads to S100A8-S100A9 protein overexpression and gliosis

Myung-Jeom Ryu1, Yangang Liu, Xiaofen Zhong

  • 1McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.

The Journal of Biological Chemistry
|May 12, 2012
PubMed

Insights

Oncogenic Kras in neurons drives gliosis by upregulating S100A8-S100A9. These secreted proteins promote astrocyte growth, suggesting an early role in tumorigenesis.

Area of Science:

  • Neuro-oncology
  • Cell signaling
  • Molecular biology

Background:

  • Ras signaling pathway hyperactivation in neurons is linked to gliosis and astrocytoma.
  • The precise molecular mechanisms driving this nonautonomous process are not fully understood.

Purpose of the Study:

  • To elucidate the mechanisms by which oncogenic Kras in neurons promotes gliosis.
  • To identify key molecular mediators involved in Kras-driven gliosis and potential astrocytoma formation.

Main Methods:

  • Generation of compound mice (LSL Kras G12D/+;CamKII-Cre) for inducible expression of oncogenic Kras in postmitotic neurons.
  • Microarray analysis to identify differentially expressed genes in mutant cortices.
  • In vitro studies using purified S100A8-S100A9 proteins to assess effects on primary astrocytes.

Main Results:

  • Mice expressing oncogenic Kras in neurons exhibited progressive gliosis associated with Ras pathway hyperactivation.
  • S100A8 and S100A9 were significantly overexpressed in neurons of mutant cortices, not myeloid cells.
  • Neuronally expressed S100A8-S100A9 promoted astrocyte growth in vitro via TLR4 and RAGE signaling, and increased microglia infiltration.

Conclusions:

  • Neuronal overexpression of S100A8-S100A9 is an early event in oncogenic Kras-induced gliosis.
  • These secreted proteins, expressed by nonhematopoietic cells, may contribute to tumorigenesis at early stages.
  • Findings reveal a novel mechanism linking neuronal oncogene activation to glial responses and potential tumor initiation.

More Related Videos

Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells12:52

Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells

Published on: November 28, 2015

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

Related Concept Videos

Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
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 superfamily...
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 daughter...
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...
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic cells are...
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 rapamycin-insensitive companion...