Scientists pinpoint a new molecular mechanism tied to pancreatic cancer

August 22, 2013 by Rob Cahill

(Medical Xpress)—New research led by scientists at The University of Texas Health Science Center at Houston (UTHealth) and Baylor College of Medicine could aid efforts to diagnose and treat one of the most lethal and hard-to-treat types of cancer.

In the EMBO Molecular Medicine journal, the investigators report that they have identified a new molecular mechanism that contributes to the spread of in the pancreas. The hope is that drugs could one day be developed to block this pathway.

Most people with die within one to two years of diagnosis and it is expected to claim 38,460 lives in the United States in 2013. There are currently no effective tests for early detection and no effective therapies for the fast-spreading form.

The study focused on the previously established link between zinc and pancreatic cancer and sought to identify a responsible for the elevated levels found in human and animal cells. Zinc is an essential trace element and small amounts are important for human health.

"We were the first to show that zinc transporter ZIP4 was a marker for pancreatic cancer," said Min Li, Ph.D., the study's senior author and associate professor and director of the Cancer Research Program in the Vivian L. Smith Department of Neurosurgery at the UTHealth Medical School. "We knew there was a link but we didn't know what it was."

Li is on the faculty of The University of Texas Graduate School of Biomedical Sciences at Houston, which is a joint venture of UTHealth and The University of Texas MD Anderson Cancer Center.

Zinc levels are regulated by ZIP4, which acts as a master switch, and the researchers designed experiments to determine what happens when the switch is flipped on, Li said.

In an animal model of pancreatic cancer, the scientists observed how the initiation of ZIP4 triggered the activation of two downstream genes, which in turn accounts for the increased . Scientists describe this as a signaling cascade.

"Pancreatic cancer is among the worst of all cancers. It is imperative to define the mechanism of this deadly disease. We have recently demonstrated a novel biological role for the zinc transporter ZIP4 in pancreatic cancer; however, the molecular pathway controlling this phenomenon remains elusive. This study provides a comprehensive mechanism for ZIP4-mediated pancreatic cancer growth involving the activation of a transcription factor CREB and an oncogenic miR-373, and reduction in key tumor suppressor genes," said Yuqing Zhang, Ph.D., co-first author of the study.

Jingxuan Yang, Ph.D., co-first author and research scientist at the UTHealth Medical School, said, "Our findings in this study define a novel signaling axis promoting pancreatic cancer growth, providing potential mechanistic insights on how a zinc transporter functions in cancer cells and may have broader implications as abnormal zinc concentration in the cells plays an important role in many other diseases."

"The results we reported in this study may help the design of future therapeutic strategies targeting the zinc transporter and microRNA pathways to treat pancreatic cancer," said Xiaobo Cui, M.D., Ph.D., study co-first author and postdoctoral research fellow at the UTHealth Medical School.

The study is titled "A novel epigenetic CREB-miR-373 axis mediates ZIP4-induced pancreatic ."

Explore further: Scientists find new molecule to target in pancreatic cancer treatment

More information: onlinelibrary.wiley.com/doi/10 … /emmm.201302507/full

Related Stories

Scientists find new molecule to target in pancreatic cancer treatment

January 3, 2013
Researchers at Mayo Clinic in Florida have identified a new target to improve treatment of pancreatic ductal adenocarcinoma cancer, which accounts for more than 95 percent of pancreatic cancer cases. This fast-growing, often ...

Researchers decode origin of inflammation-driven pancreatic cancer

August 5, 2013
Researchers at Mayo Clinic in Florida have revealed the process by which chronic inflammation of the pancreas, pancreatitis, morphs into pancreatic cancer. They say their findings point to ways to identify pancreatitis patients ...

Scientists find potential loophole in pancreatic cancer defenses

March 27, 2013
Dana-Farber Cancer Institute scientists and colleagues have discovered that pancreatic cancer cells' growth and spread are fueled by an unusual metabolic pathway that someday might be blocked with targeted drugs to control ...

Nerve growth factors elevated in pancreatic cancer model

June 19, 2012
Severe pain is a major symptom of pancreatic cancer. The results of a new study show that four different factors involved in the growth and maintenance of nerves are elevated in a mouse model of pancreatic cancer. This is ...

Researcher examines mechanism underlying abdominal pain in pancreatic cancer

March 1, 2013
Erxi Wu, assistant professor of pharmaceutical sciences, co-wrote the article, "Neurotransmitter substance P mediates pancreatic cancer perineural invasion via NK-1R in cancer cells," which was published by Molecular Cancer ...

Recommended for you

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.

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

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.