Self-perpetuating signals may drive tumor cells to spread

July 16, 2013, Johns Hopkins University School of Medicine

A team of international researchers from Duke-NUS Graduate Medical School Singapore and the Johns Hopkins University School of Medicine (USA) has identified a self-perpetuating signaling circuit inside connective tissue cells that allows these cells to form a front and a back and propel themselves in a particular direction over a long period of time. This propulsion is the same movement that tumor cells use to invade healthy tissue during cancer metastasis so cracking the code to this signaling network may lead to new therapeutic strategies against cancer and other devastating diseases.

Many different types of cells in our body can crawl and migrate to distinct locations, sometimes over long distances. Immune system cells, for example, move to a wound site to kill microorganisms during an infection, and (fibroblasts) move there to repair damaged areas. Cell migration is essential to a variety of biological processes, such as the development of an organism, wound healing, and , but also the invasion of during cancer metastasis.

Cell migration is an extraordinarily complex process which depends on the ability of a cell to form a front and a back (called polarization) and generate force in one . Migrating cells are able to do this spontaneously, without assistance from the environment. How they do this is a question that has kept busy for the .

These latest results shed light on the migratory mechanism of cells. In particular, the team found that the signaling network involved has an interesting property, well known to engineers and bankers: it is self-perpetuating. A classic analogy to this type of circuit is a bank run, which occurs when a large number of customers withdraw their money from a bank due to concerns about the bank's solvency. As more people withdraw their funds, the probability of default increases, prompting more people to withdraw their money, in a kind of self-fulfilling prophecy (or positive feedback loop).

The team went on to show that this positive feedback circuit is switched on in very specific regions in the connective tissue cells, causing proteins to push against only one side of the outer envelope of the cell, eventually causing movement in one preferred direction. Predictably, two important protein components of this signaling circuit, called Ras and PI3K, are often mutated in cancer. This suggests that misregulation of this circuit may increase the invasiveness of cancer cells. It also highlights the need to understand how signaling proteins interact with each other inside cells, hopefully leading one day to new therapies for cancer and other deadly diseases.

This study, entitled "The small GTPase HRas shapes local PI3K signals through positive feedback and regulates persistent membrane extension in migrating fibroblasts" was published online in Molecular Biology of the Cell on May 15. It is supported by a grant from the Ministry of Education.

Explore further: 'Chase and run' cell movement mechanism explains process of metastasis

Related Stories

'Chase and run' cell movement mechanism explains process of metastasis

June 16, 2013
A mechanism that cells use to group together and move around the body – called 'chase and run' - has been described for the first time by scientists at UCL.

Stopping cell migration may help block fibrosis and the spread of cancer

May 21, 2012
(Medical Xpress) -- Discoveries by a Yale-led team of scientists could lead the way for development of new therapies for treating fibrosis and tumor metastasis. The researchers have both uncovered a signaling pathway that ...

Protein is involved with colon cancer cell's ability to invade other cells

June 27, 2013
Understanding how the protein km23-1 enables in the spread of colon cancer may lead to new treatments for the disease, according to researchers at Penn State College of Medicine.

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 ...

Gene variant may provide novel therapy for several cancer types

June 7, 2013
(Medical Xpress)—A novel gene variant found in human and animal tissue may be a promising treatment for cancer, including breast and brain cancer, according to scientists from the Icahn School of Medicine at Mount Sinai. ...

Recommended for you

Study: Cells of three advanced cancers die with drug-like compounds that reverse chemo failure

January 23, 2018
Researchers at Southern Methodist University have discovered three drug-like compounds that successfully reverse chemotherapy failure in three of the most commonly aggressive cancers—ovarian, prostate and breast.

'Hijacker' drives cancer in some patients with high-risk neuroblastoma

January 23, 2018
Researchers have identified mechanisms that drive about 10 percent of high-risk neuroblastoma cases and have used a new approach to show how the cancer genome "hijacks" DNA that regulates other genes. The resulting insights ...

Scientists block the siren call of two aggressive cancers

January 23, 2018
Aggressive cancers like glioblastoma and metastatic breast cancer have in common a siren call that beckons the bone marrow to send along whatever the tumors need to survive and thrive.

Enzyme inhibitor combined with chemotherapy delays glioblastoma growth

January 23, 2018
In animal experiments, a human-derived glioblastoma significantly regressed when treated with the combination of an experimental enzyme inhibitor and the standard glioblastoma chemotherapy drug, temozolomide.

Researchers identify a protein that keeps metastatic breast cancer cells dormant

January 23, 2018
A study headed by ICREA researcher Roger Gomis at the Institute for Research in Biomedicine (IRB Barcelona) has identified the genes involved in the latent asymptomatic state of breast cancer metastases. The work sheds light ...

Boosting cancer therapy with cross-dressed immune cells

January 22, 2018
Researchers at EPFL have created artificial molecules that can help the immune system to recognize and attack cancer tumors. The study is published in Nature Methods.

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.