Gene discovery links cancer cell 'recycling' system to potential new therapy

May 1, 2014, University of Rochester Medical Center

University of Rochester scientists have discovered a gene with a critical link to pancreatic cancer, and further investigation in mice shows that by blocking the gene's most important function, researchers can slow the disease and extend survival.

Published online by Cell Reports, the finding offers a potential new route to intrude on a cancer that usually strikes quickly, has been stubbornly resistant to targeted therapies, and has a low survival rate. Most recent improvements in the treatment of , in fact, are the result of using different combinations of older chemotherapy drugs. The research led by Hartmut "Hucky" Land, Ph.D., and Aram F. Hezel, M.D., of UR Medicine's James P. Wilmot Cancer Center, identifies a new target in the process of garbage recycling that occurs within the cancer cell called autophagy, which is critical to pancreatic and growth.

Autophagy is derived from the Greek roots "auto" (self) and "phagein" (to eat), and is an intracellular digestive process that allows cells to survive under stress. During a cell's transformation from normal to malignant, autophagy speeds up to keep pace with rapid cellular changes and a tumor's quest to grow. The newly discovered PLAC-8 gene sustains the highly active recycling process, as it removes faulty proteins and organelles and degrades them into reusable building blocks during cancer progression.

"What makes this an exciting opportunity is that the gene we're studying is critical to the cancer cell's machinery but it is not essential to the function of normal cells," said Land, chair of Biomedical Genetics at the University of Rochester School of Medicine and Dentistry and director of research at Wilmot. "By targeting these types of non-mutated genes that are highly specific to cancer, we are looking for more effective ways to intervene."

The Cell Reports study underlines Wilmot's overall unique approach to . Rather than investigate single faulty genes linked to single subtypes of cancer, Rochester scientists have identified a larger network of approximately 100 non-mutated genes that cooperate and control the shared activities of many cancers. While investigating this larger gene network, Land and Hezel focused on PLAC-8.

Moreover, the team found that by inactivating PLAC-8 in mice and shutting down autophagy, they could significantly slow cancer's progression. The relevance of PLAC-8 may also extend to other tumors – lung, colon, and liver, for example—that share key genetic changes such as KRAS and p53 mutations that are present in the majority of pancreatic cancers. The breadth of these findings is an area of ongoing study in the Land and Hezel labs.

"PLAC-8 and its job within the cancer cell of accelerating recycling suggests new points of attack and what we all hope will be opportunities to identify and develop new treatments," said Hezel, vice chief of Wilmot's Division of Hematology and Oncology and a UR associate professor. "Our data showing PLAC 8's role in autophagy has great potential because while there are other drugs being evaluated to inhibit autophagy, not all of them target proteins specifically important to this process in tumors."

The role of autophagy in cancer is gaining attention. Clinical testing of new therapies is taking place at the same time that a new basic understanding of this process and how it functions in pancreatic cancer is emerging.

The New England Journal of Medicine recently published a commentary on 's role in pancreatic cancer and the possible implications for clinical trials. And the Rochester paper offers explanations for some discrepancies seen in previous studies; Cell Reports invited Land and Hezel to write an online blog to accompany their article, describing their data in light of the scientific questions.

Explore further: Zombie cancer cells eat themselves to live

Related Stories

Zombie cancer cells eat themselves to live

April 5, 2014
A University of Colorado Cancer Center study recently published in the journal Cell Reports and presented today at the American Association for Cancer Research (AACR) Annual Conference 2014 shows that the cellular process ...

Interference with cellular recycling leads to cancer growth, chemotherapy resistance

September 18, 2013
Overactivity of a protein that normally cues cells to divide sabotages the body's natural cellular recycling process, leading to heightened cancer growth and chemotherapy resistance, UT Southwestern Medical Center researchers ...

Autophagy predicts which cancer cells live and die when faced with anti-cancer drugs

January 10, 2014
(Medical Xpress)—When a tumor is treated with an anti-cancer drug, some cells die and, unfortunately, some cells tend to live. A University of Colorado Cancer Center study published in the journal Nature Cell Biology details ...

Autophagy-addicted breast cancers killed by anti-malaria drug, chloroquine

April 8, 2013
The process of autophagy cleans cells – they wrap up the bad stuff and then dispose of it. And so it stands to reason that inhibiting autophagy would make cancer cells less able to cleanse themselves of chemotherapy and ...

Novel drug cocktail may improve clinical treatment for pancreatic cancer

May 1, 2014
Pancreatic cancer is the fourth leading cause of cancer deaths in the U.S. and has the lowest overall survival rate of all major cancers (~6%). With current treatment options being met with limited success it is anticipated ...

Jamming a protein signal forces cancer cells to devour themselves

April 3, 2014
Under stress from chemotherapy or radiation, some cancer cells dodge death by consuming a bit of themselves, allowing them to essentially sleep through treatment and later awaken as tougher, resistant disease.

Recommended for you

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.

Workouts may boost life span after breast cancer

January 22, 2018
(HealthDay)—Longer survival after breast cancer may be as simple as staying fit, new research shows.

Cancer patients who tell their life story find more peace, less depression

January 22, 2018
Fifteen years ago, University of Wisconsin–Madison researcher Meg Wise began interviewing cancer patients nearing the end of life about how they were living with their diagnosis. She was surprised to find that many asked ...

Single blood test screens for eight cancer types

January 18, 2018
Johns Hopkins Kimmel Cancer Center researchers developed a single blood test that screens for eight common cancer types and helps identify the location of the cancer.

Researchers find a way to 'starve' cancer

January 18, 2018
Researchers at Vanderbilt University Medical Center (VUMC) have demonstrated for the first time that it is possible to starve a tumor and stop its growth with a newly discovered small compound that blocks uptake of the vital ...

How cancer metastasis happens: Researchers reveal a key mechanism

January 18, 2018
Cancer metastasis, the migration of cells from a primary tumor to form distant tumors in the body, can be triggered by a chronic leakage of DNA within tumor cells, according to a team led by Weill Cornell Medicine and Memorial ...

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.