Scientists discover new link in pathway to cancer: hope for drug design

August 28, 2008

( -- University of Manchester scientists have identified an exciting connection between a cell’s extracellular environment and the activity of a signalling pathway molecule that controls the development of organs and tissues, as well as cancer and kidney disease.

Dr Hilary Ashe and her team at the Faculty of Life Sciences hope their work will help develop drugs targeting the pathway, which is known to be involved in 90% of pancreatic cancers and 60% of colorectal cancers, or to activate the pathway and thus reverse kidney disease.

Their study, published in Nature (August 2008), showed that human type IV collagen in the extracellular matrix around the cells binds a human BMP signalling molecule.

During development cells communicate with each other by releasing signalling molecules (chemical signals). Other cells receive and interpret these signals in order to determine which type of tissue or organ they will form.

The signalling molecules which exist in the fruitfly Drosophila melanogaster are the same as those which control development in humans. BMP signalling molecules are one of the major signals used during human and fly development. In humans, BMP signalling is necessary for the development of many major tissues and organs, such as the nervous system, kidney, lungs and skin.

In addition cells are surrounded by a network of proteins called an extracellular matrix with one form consisting of type IV collagen proteins. The relationship between type IV collagen and the BMP signalling molecule formed the basis of the BBSRC-funded study.

Dr Ashe explained: “Our study has shown that BMP signalling molecules released by cells bind to the type IV collagen extracellular matrix. As a result, type IV collagens regulate the movement of BMP molecules and their ability to signal after they are released by cells. Therefore type IV collagens control the level of BMP signalling molecules that cells become exposed to, which in turn determines cell identity.

“We have also shown that human type IV collagen binds a human BMP signalling molecule, suggesting that the regulation also exists in vertebrates.”

She added: “As alterations in the activity of BMP and type IV collagen molecules can lead to cancer and kidney diseases respectively, our data will ultimately have important implications for human disease.

“The BMP signalling pathway initially acts as a tumour suppressor but when a tumour becomes malignant, it uses the pathway to become aggressive and spread to other parts of the body. The numbers are incredible – we know that 90% of pancreatic cancers and 60% of colorectal cancers will have an alteration in this signalling pathway.

“In addition part of the collagen we have identified as important has tumour suppressor activity so we believe that when the BMP pathway is being exploited by aggressive tumours the collagens are counteracting this. This is another facet to be investigated.

“Finally type IV collagen is also important in kidney development and disease. This signalling pathway promotes kidney development and kidney disease is caused by disruptions to these collagens. In fact a previous study has shown that if you make this pathway more active you can reverse kidney disease, so further work could help design therapies in this area as well.

“This study has given us a new area to manipulate, making tumours more or less aggressive, by controlling how active this pathway is. In the future we could see compounds that are designed to make the regulation stronger, to work against a tumour or reverse kidney disease.”

Provided by University of Manchester

Explore further: Research redefines proteins' role in the development of spinal sensory cells

Related Stories

Research redefines proteins' role in the development of spinal sensory cells

September 19, 2017
A recent study led by Samantha Butler at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA has overturned a common belief about how a certain class of proteins in the spinal cord regulate ...

One signal means different things to stem cells versus their progeny

October 14, 2014
Two listeners might hear the same message, but understand it differently and take different actions in response. Something similar happens within the hair follicle: Stem cells and their progeny react quite differently to ...

Researchers describe new molecular interactions behind the inhibition of TGF beta-signaling

August 24, 2012
(—Researchers headed by Maria Macias an ICREA researcher at the Institute for Research in Biomedicine (IRB Barcelona) and Joan Massagué, a Howard Hughes Medical Institute investigator at Memorial Sloan-Kettering ...

Study links signalling protein to osteoarthritis

March 1, 2016
Researchers show that the protein CCN4 positively regulates the generation of cartilage matrix, which are depleted in osteoarthritis.

How major signaling pathways are wired to our genome gives new insight into disease processes

October 27, 2011
Whitehead Institute scientists have determined that master transcription factors determine the genes regulated by key signaling pathways. In this way, signaling pathways are targeted to genes that are most relevant to each ...

Researchers identify signals during embryonic development that control the fate of skin cells to be sweaty or hairy

December 23, 2016
(Medical Xpress)—A team of researchers with the Rockefeller University has identified the signals and timing that are involved during embryonic development controlling whether skin cells grow to be sweaty or hairy. In their ...

Recommended for you

Lung cancer triggers pulmonary hypertension

November 17, 2017
Shortness of breath and respiratory distress often increase the suffering of advanced-stage lung cancer patients. These symptoms can be triggered by pulmonary hypertension, as scientists at the Max Planck Institute for Heart ...

Researchers discover an Achilles heel in a lethal leukemia

November 16, 2017
Researchers have discovered how a linkage between two proteins in acute myeloid leukemia enables cancer cells to resist chemotherapy and showed that disrupting the linkage could render the cells vulnerable to treatment. St. ...

Computer program finds new uses for old drugs

November 16, 2017
Researchers at the Case Comprehensive Cancer Center at Case Western Reserve University School of Medicine have developed a computer program to find new indications for old drugs. The computer program, called DrugPredict, ...

Pharmacoscopy improves therapy for relapsed blood cancer in a first clinical trial

November 16, 2017
Researchers at CeMM and the Medical University of Vienna presented a preliminary report in The Lancet Hematology on the clinical impact of an integrated ex vivo approach called pharmacoscopy. The procedures measure single-cell ...

Wider sampling of tumor tissues may guide drug choice, improve outcomes

November 15, 2017
A new study focused on describing genetic variations within a primary tumor, differences between the primary and a metastatic branch of that tumor, and additional diversity found in tumor DNA in the blood stream could help ...

A new strategy for prevention of liver cancer development

November 14, 2017
Primary liver cancer is now the second leading cause of cancer-related death worldwide, and its incidences and mortality are increasing rapidly in the United Stated. In late stages of the malignancy, there are no effective ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

1 / 5 (1) Aug 28, 2008
OH! It's a long, long pathway before chemists discover the nature of the signals! They are ELECTRONS - whose spin and speed carry the message! A few physicists in the lab could learn to read, and alter the messages!

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.