Researchers discover master regulator in cancer metastasis

June 10, 2013
Mammary epithelial cells that have undergone an epithelial-mesenchymal transition, exhibit a change in cell morphology with actin stress fibers (red) and with focused cell adhesion points (green). Credit: Dr. Nathalie Meyer-Schaller, University of Basel

In the process of metastasis, the movement of cancer cells to different parts of the body, a specific master regulator gene plays a central role: a transcription factor named Sox4 activates a sequence of genes and triggers the formidable process. This finding is reported by researchers from the University of Basel and from the Friedrich Miescher Institute in Cancer Cell. Inhibition of Sox4 and subsequent processes may prevent metastasis in cancer patients.

The predominant cause of death in is metastasis, the formation of secondary tumors in other organs like the brain, liver, and lungs. detach from the original primary tumor and reach a single cell or group of cells in another organ. The cells of the body normally remain in place through adhering to an extracellular substance. However, cancer cells learn how to release themselves from these bonds and invade surrounding tissues, blood, and the lymphatic system.

The transformation of sedentary, specialized cells into wandering, invasive, and unspecialized cells is called epithelial-mesenchymal transition (EMT), which is central to metastasis. EMT is a multistage process, which is accompanied by a fundamental change in and number of genetic programs. The that govern EMT, however, are still poorly understood.

Main Switch Found

The research groups of Prof. Gerhard Christofori of the Department of Biomedicine at the University of Basel; Prof. Erik van Nimwegen from the Biozentrum, University of Basel; and Prof. Dirk Schuebeler from the Friedrich Miescher Institute have discovered a master regulator of EMT and metastasis: the transcription factor Sox4 is upregulated in its activity and triggers the expression of a number of genes that play an important role during EMT and metastasis.

In particular, Sox4 promotes the expression of the enzyme Ezh2, a methyltransferase, which generally influences methylation of specific proteins (histones), the packaging of the genetic material, and thus its readability and gene expression. Due to this change in genetic information, the behavior and function of cells are reprogrammed - a process that is currently observed during metastasis. Such a change in gene expression is also found in patients with malignant cancer and metastasis and correlates with a poor prognosis.

These findings point to the possibility that the inhibition of the transcription factor Sox4 and especially the Ezh2 could hinder metastasis in cancer patients. Appropriate medications are currently being developed but they need to undergo clinical trials before being used in patients. The research was implemented within the framework of the SystemsX.ch-RTD Project "Cell Plasticity."

Explore further: Six2 homeoprotein allows breast cancer cells to detach and metastasize

More information: Neha Tiwari, Vijay K. Tiwari, Lorenz Waldmeier, Piotr J. Balwierz, Phil Arnold, Mikhail Pachkov, Nathalie Meyer-Schaller, Dirk Schübeler, Erik van Nimwegen, and Gerhard Christofori, Sox4 Is a Master Regulator of Epithelial-Mesenchymal Transition by Controlling Ezh2 Expression and Epigenetic Reprogramming Cancer Cell; Published online June 10, 2013.

Related Stories

Six2 homeoprotein allows breast cancer cells to detach and metastasize

April 9, 2013
In results presented at the AACR Annual Meeting 2013, researchers from the University of Colorado Cancer Center show that the Six2 homeoprotein, while not involved in primary tumor growth, allows cells to detach from substrate ...

Study helps resolve debate about how tumors spread

November 29, 2012
A team of scientists, led by researchers at the University of California, San Diego School of Medicine, has shown for the first time how cancer cells control the ON/OFF switch of a program used by developing embryos to effectively ...

Researchers discover protein that may control the spread of cancer

February 26, 2013
Researchers at the University of Hawai'i Cancer Center have uncovered a novel mechanism that may lead to more selective ways to stop cancer cells from spreading. Associate Professor Joe W. Ramos PhD, a cancer biologist at ...

Transition in cell type parallels treatment response, disease progression in breast cancer

January 31, 2013
A process that normally occurs in developing embryos – the changing of one basic cell type into another – has also been suspected of playing a role in cancer metastasis. Now a study from Massachusetts General Hospital ...

New study shows promise for developing new treatments for breast cancer

March 14, 2012
A new study by University of Kentucky researchers provides insight into developing new treatment strategies for basal-like breast cancer, commonly known as triple-negative breast cancer. This cancer is associated with early ...

Tracking the cell transitions that cause cancer

March 6, 2013
Researchers think that for cancer to develop, damaged cells have to undergo certain transitions that cause them to spread, or metastasize. Junior Tristan Bepler, a biology and computer science major, is testing this hypothesis, ...

Recommended for you

Study prompts new ideas on cancers' origins

December 16, 2017
Rapidly dividing, yet aberrant stem cells are a major source of cancer. But a new study suggests that mature cells also play a key role in initiating cancer—a finding that could upend the way scientists think about the ...

What does hair loss have to teach us about cancer metastasis?

December 15, 2017
Understanding how cancer cells are able to metastasize—migrate from the primary tumor to distant sites in the body—and developing therapies to inhibit this process are the focus of many laboratories around the country. ...

Cancer immunotherapy may work better in patients with specific genes

December 15, 2017
Cancer cells arise when DNA is mutated, and these cells should be recognized as "foreign" by the immune system. However, cancer cells have found ways to evade detection by the immune system.

Scientists pinpoint gene to blame for poorer survival rate in early-onset breast cancer patients

December 15, 2017
A new study led by scientists at the University of Southampton has found that inherited variation in a particular gene may be to blame for the lower survival rate of patients diagnosed with early-onset breast cancer.

Scientists unlock structure of mTOR, a key cancer cell signaling protein

December 14, 2017
Researchers in the Sloan Kettering Institute have solved the structure of an important signaling molecule in cancer cells. They used a new technology called cryo-EM to visualize the structure in three dimensions. The detailed ...

'Bet hedging' explains the efficacy of many combination cancer therapies

December 14, 2017
The efficacy of many FDA-approved cancer drug combinations is not due to synergistic interactions between drugs, but rather to a form of "bet hedging," according to a new study published by Harvard Medical School researchers ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.