Related Experiment Video

Updated: Jul 5, 2026

Reliably Engineering and Controlling Stable Optogenetic Gene Circuits in Mammalian Cells
09:20

Reliably Engineering and Controlling Stable Optogenetic Gene Circuits in Mammalian Cells

Published on: July 6, 2021

Explaining the preponderance of Kras mutations in human cancer: An isoform-specific function in stem cell expansion

Margaret P Quinlan1, Jeffrey Settleman

  • 1Center for Molecular Therapeutics, Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachussets, USA.

Cell Cycle (Georgetown, Tex.)
|April 18, 2008
PubMed

Insights

Mutant Kirsten rat sarcoma viral oncogene homolog (Kras) uniquely promotes the expansion and blocks differentiation of endodermal stem cells. This may explain why Kras mutations are common in cancers of endodermal tissues like the pancreas, lung, and colon.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Stem Cells

Background:

  • Ras proteins (Kras, Hras, Nras) are closely related isoforms that can drive oncogenesis when mutationally activated.
  • Activated Ras alleles are frequently found in human cancers, with mutant Kras being the most prevalent.
  • Mutant Kras is particularly enriched in tumors originating from endodermal tissues, such as pancreas, lung, and colon.

Purpose of the Study:

  • To investigate the unique role of Kras in cancer initiation within endodermally-derived tissues.
  • To elucidate the specific mechanisms by which activated Kras may contribute to tumorigenesis.
  • To understand why Kras mutations are more common than Hras or Nras mutations in certain cancer types.

Main Methods:

  • Comparative analysis of oncogenic activity among Kras, Hras, and Nras isoforms.
  • In vitro and/or in vivo studies assessing the effects of activated Kras on endodermal stem/progenitor cell behavior.
  • Examination of differentiation pathways in response to activated Kras signaling.

Main Results:

  • Activated Kras, unlike activated Hras or Nras, was observed to promote the expansion of endodermal stem/progenitor cells.
  • Activated Kras was found to inhibit the differentiation of these stem/progenitor cells.
  • These findings suggest a distinct mechanism for Kras in initiating tumors within endodermal lineages.

Conclusions:

  • Kras possesses unique properties that facilitate the expansion of a stem/progenitor cell population in endodermal tissues.
  • This expansion of stem/progenitor cells by Kras may be a critical early step in the initiation of cancers in the pancreas, lung, and colon.
  • The specific effects of Kras on endodermal stem cell biology provide a potential explanation for its frequent mutation in associated cancers.

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

Evaluation of Abnormal Growth-related Genes of Hematopoietic Stem and Progenitor Cells by Combining CRISPR/Cas9 Technology with Cell Counting07:01

Evaluation of Abnormal Growth-related Genes of Hematopoietic Stem and Progenitor Cells by Combining CRISPR/Cas9 Technology with Cell Counting

Published on: May 2, 2025

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 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...
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...
Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...