Role of rogue protein PAK4 confirmed in pancreatic cancer cells

February 17, 2017
Axial CT image with i.v. contrast. Macrocystic adenocarcinoma of the pancreatic head. Credit: public domain

A new study that confirms the role of a protein called PAK4 in the movement and growth of pancreatic cancer cells could help researchers find new ways to tackle the disease.

The work, funded by national charity Pancreatic Cancer Research Fund, uncovers new evidence that PAK4 plays a key role in enabling to grow and to spread from the pancreas into other areas of the body, a process called metastasis.

The researchers, from Kings College London, also found evidence of a close relationship between PAK4 and a well-researched cancer pathway called the phosphoinositide 3-kinase pathway (PI3K). PI3K is responsible for regulating the growth and survival of cancer cells and several inhibitors targeting it have already been developed.

"We've seen hints before that PAK4 and PI3K pathway are linked, but finding evidence of their interaction is an important advance because it gives us additional avenues to explore in testing promising new inhibitor compounds that can tackle this disease," says Dr Claire Wells, who led the study. "Such studies could lead the way to thinking about combination therapy that could target both PAK4 and PI3K"

PAK4 is found at particularly high levels in pancreatic cancer cells and this work forms part of a wider investigation into the precise role of this protein in cancer progression. Dr Wells' team has previously published research on the importance of PAK4 in other types of cancer, including prostate, breast and melanoma.

The work complements existing studies into PAK4, but advances existing knowledge by using a sophisticated model system that better mimics a pancreatic tumour, alongside films of the cells as they grow and develop.

The team also studied what happened when PAK4 was removed from the cells, using an RNA silencing technology that can prevent production of specific proteins.

"This technique allows us to look in detail at the structure and development of the cells, and we can clearly see that, if you remove PAK4 from those cells, they lose their ability to be really invasive," explains Dr Wells.

"One of the big problems with pancreatic cancer is recurrence - even for people who can have surgery, there's a really high level of recurrence," adds Dr Wells. "If we can develop therapeutics that would suppress the movement of cells out of the pancreas, they could be given to patients following surgery and help to prevent that recurrence and spread of the disease."

Ultimately this research confirms PAK4 as a promising target for new drug compounds, a number of which have already been identified by the researchers for testing. The team is also planning further research to find out more about why cells rely on PAK4 and what other proteins and pathways PAK4 is interacting with to drive cell growth and migration.

Explore further: Study challenges potential pancreatic cancer target

More information: Helen King et al, PAK4 interacts with p85 alpha: implications for pancreatic cancer cell migration, Scientific Reports (2017). DOI: 10.1038/srep42575

Related Stories

Study challenges potential pancreatic cancer target

January 17, 2017
A protein thought to fuel pancreatic cancer development plays a much more complicated role, a new study finds.

Reason for pancreatic cancer's resistance to chemotherapy found

November 21, 2016
A pioneering University of Liverpool research team have published a study that identifies the mechanism in the human body that causes resistance of pancreatic cancer cells to chemotherapy.

The PI3K protein: A potential new therapeutic target in pancreatic neuroendocrine tumors

June 20, 2016
Researchers at the Institute of Biomedical Investigation of Bellvitge (IDIBELL), led by Dr. Mariona Graupera, have unveiled the potential therapeutic benefit of a selective inhibitior of the PI3-kinase (PI3K) protein in pancreatic ...

Starving pancreatic cancer cells: Scientists identify potential pancreatic cancer target

October 17, 2016
Researchers have found that a protein called SLC6A14 is overexpressed by several fold in pancreatic tumors taken from patients and in cancerous pancreatic cells lines compared with normal pancreatic tissue or normal pancreatic ...

Aspirin slows growth of colon, pancreatic tumor cells

December 15, 2016
Researchers from Oregon Health and Science University and Oregon State University have found that aspirin may slow the spread of some types of colon and pancreatic cancer cells. The paper is published in the American Journal ...

Recommended for you

Targeted antibiotic use may help cure chronic myeloid leukaemia

September 19, 2017
The antibiotic tigecycline, when used in combination with current treatment, may hold the key to eradicating chronic myeloid leukaemia (CML) cells, according to new research.

Brain powered: Increased physical activity among breast cancer survivors boosts cognition

September 19, 2017
It is estimated that up to 75 percent of breast cancer survivors experience problems with cognitive difficulties following treatments, perhaps lasting years. Currently, few science-based options are available to help. In ...

Researchers compose guidelines for handling CAR T cell side effects

September 19, 2017
Immune-cell based therapies opening a new frontier for cancer treatment carry unique, potentially lethal side effects that provide a new challenge for oncologists, one addressed by a team led by clinicians at The University ...

Bone marrow protein a 'magnet' for passing prostate cancer cells

September 19, 2017
Scientists at the University of York have shown that a protein in the bone marrow acts like a 'magnetic docking station' for prostate cancer cells, helping them grow and spread outside of the prostate.

Brain cancer breakthrough could provide better treatment

September 19, 2017
A new discovery about the most common type of childhood brain cancer could transform treatment for young patients by enabling doctors to give the most effective therapies.

A new paradigm for treating transcription factor-driven cancers

September 18, 2017
In the current issue of Proceedings of the National Academy of Sciences, researchers from Nationwide Children's Hospital describe a new paradigm for treating transcription factor-driven cancers. The study focuses on Ewing ...

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.