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

Study may explain failure of retinoic acid trials against breast cancer

July 25, 2017
Estrogen-positive breast cancers are often treated with anti-estrogen therapies. But about half of these cancers contain a subpopulation of cells marked by the protein cytokeratin 5 (CK5), which resists treatment—and breast ...

Physical activity could combat fatigue, cognitive decline in cancer survivors

July 25, 2017
A new study indicates that cancer patients and survivors have a ready weapon against fatigue and "chemo brain": a brisk walk.

Breaking the genetic resistance of lung cancer and melanoma

July 25, 2017
Researchers from Monash University and the Memorial Sloan Kettering Cancer Center (MSKCC, New York) have discovered why some cancers – particularly lung cancer and melanoma – are able to quickly develop deadly resistance ...

New therapeutic approach for difficult-to-treat subtype of ovarian cancer identified

July 24, 2017
A potential new therapeutic strategy for a difficult-to-treat form of ovarian cancer has been discovered by Wistar scientists. The findings were published online in Nature Cell Biology.

Immune cells the missing ingredient in new bladder cancer treatment

July 24, 2017
New research offers a possible explanation for why a new type of cancer treatment hasn't been working as expected against bladder cancer.

Anti-cancer chemotherapeutic agent inhibits glioblastoma growth and radiation resistance

July 24, 2017
Glioblastoma is a primary brain tumor with dismal survival rates, even after treatment with surgery, chemotherapy and radiation. A small subpopulation of tumor cells—glioma stem cells—is responsible for glioblastoma's ...

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.