Dynamics of metastasis suppressor gene inactivation

Related Experiment Video

Updated: Aug 11, 2026

A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
07:41

A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis

Published on: March 8, 2022

Franziska Michor1, Yoh Iwasa

  • 1Harvard Society of Fellows, Harvard Program for Evolutionary Dynamics, Cambridge, MA 02138, USA. michor@fas.harvard.edu

Journal of Theoretical Biology
|February 25, 2006
PubMed

Insights

Metastasis suppressor genes (MSGs) control cancer spread. Mathematical modeling reveals that most metastasis-causing mutations originate from widespread genetic changes within the primary tumor, not rare events.

Area of Science:

  • Oncology
  • Cancer Metastasis Research
  • Mathematical Biology

Background:

  • Metastasis acquisition renders most cancers clinically incurable.
  • Twelve metastasis suppressor genes (MSGs) are known to reduce cancer cell metastatic potential.
  • Inactivation of both alleles of MSGs promotes metastatic ability.

Purpose of the Study:

  • To develop a mathematical model for MSG inactivation dynamics.
  • To calculate the expected number of metastases formed by a tumor.
  • To analyze the impact of mutation rates and cell fitness on metastasis formation.

Main Methods:

  • Development of a mathematical model simulating MSG inactivation.
  • Calculation of expected metastasis numbers based on model dynamics.
  • Analysis of mutation rates and fitness effects on metastatic potential.

Main Results:

  • Mutations negatively selected in the primary tumor are unlikely to drive widespread metastasis.
  • The majority of metastasis-causing mutations are likely present in most or all cells of the primary tumor.
  • Model predicts the number of metastases based on MSG inactivation dynamics.

Conclusions:

  • Understanding MSG inactivation dynamics is crucial for predicting cancer metastasis.
  • Widespread genetic alterations in the primary tumor are key drivers of metastasis.
  • This model provides insights into the genetic basis of metastatic disease.

More Related Videos

An Orthotopic Murine Model of Human Prostate Cancer Metastasis06:48

An Orthotopic Murine Model of Human Prostate Cancer Metastasis

Published on: September 18, 2013

An In Vitro System to Study Tumor Dormancy and the Switch to Metastatic Growth09:14

An In Vitro System to Study Tumor Dormancy and the Switch to Metastatic Growth

Published on: August 11, 2011

Related Concept Videos

Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
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...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

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...
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.