Scientists identify protein key to breast cancer spread, potential new drug target

April 9, 2007

Researchers at the Kimmel Cancer Center at Jefferson have identified a protein that they say is key to helping a quarter of all breast cancers spread. The finding, reported online the week of April 9, 2007 in the journal Proceedings of the National Academy of Sciences, could be a potential target for new drugs aimed at stopping or slowing the growth and progression of breast cancer.

Kimmel Cancer Center director Richard Pestell, M.D., Ph.D., professor and chair of cancer biology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, and colleagues genetically engineered mice to lack the protein Akt1, which normally plays a role in keeping cells alive by interfering with programmed cell death. Breast and other cancers make an overabundance of the protein, and it’s thought to potentially affect survival of breast and other cancer cells as well.

To test that hypothesis, Dr. Pestell and his team bred the mice missing the gene for Akt1 with other mice that overexpressed the HER2-neu (ErbB2) oncogene, which leads to approximately 25 percent of all breast cancers. They then examined the role of Akt in the onset and progression of breast cancer in the resulting offspring.

To their surprise, mice lacking two copies of the gene that produces Akt1 rarely had any tumors. Those mice that carried only one copy of the Akt1 gene developed some tumors, but they were small and developed more slowly. Mice with two copies of Akt1 rapidly developed significant cancer.

“The finding was exciting because it told us that Akt1 is a potentially useful target for ErbB2-positive breast cancer,” Dr. Pestell says. “More interesting was that even if the mouse developed a tumor, it didn’t develop metastases. We proved that there was a requirement for Akt1 in metastasis, which makes Akt1 an exciting target for metastatic breast cancer. We knew that Akt1 could play a role in cell growth and size, but the idea that it could play a role in migration and metastasis was an unexpected new finding,”

The researchers also proved how, showing that Akt1 causes the cancer cells to secrete a factor – CXCL16 – that promotes breast cancer cell migration. Without Akt, cancer cells failed to migrate. They also showed that deleting Akt1 completely blocked breast cancer metastasis to the lungs, while mice that expressed Akt1 died from lung metastasis.

While scientists have looked at Akt as a drug target, notes Arthur Pardee, Ph.D., professor emeritus of medical oncology at the Dana-Farber Cancer Institute in Boston, its role in metastasis is less emphasized. “Blocking this with anti-Akt drugs might provide a novel treatment, especially against early cancers,” he says.

While the monoclonal antibody drug Herceptin has been very successful in treating ErbB2-positive breast cancer, patients can relapse, Dr. Pestell notes, and other drug targets are needed. The newly found secreted factor may prove to be such a target.

Source: Thomas Jefferson University

Explore further: Investigational AKT inhibitor AZD5363 is active against multiple tumor types with AKT1 E17K mutations

Related Stories

Investigational AKT inhibitor AZD5363 is active against multiple tumor types with AKT1 E17K mutations

November 9, 2015
Treatment with the investigational pan-AKT inhibitor AZD5363 led to tumor regression in patients with a variety of types of solid tumors positive for the AKT1 E17K genetic mutation, according to data from a phase I clinical ...

Genetic alterations in treatment-resistant metastatic breast cancer found to be distinct from those in primary tumors

December 9, 2016
Drug-resistant, estrogen-fueled breast cancers that have spread beyond their initial site often have different genetic alterations than the original tumors, according to a large-scale tumor-tissue analysis led by Dana-Farber ...

Malignant stem cells may explain why some breast cancers develop and recur

August 16, 2011
Mutations that are found in stem cells could be causing some breast cancers to develop and may be the reason the disease recurs. These abnormal cells are likely controlling cell functions in the tumor and, given they are ...

Study discovers breast cancer metastasis gene

August 11, 2015
Monash researchers have discovered an entirely new gene, responsible for triggering breast cancer, increasing tumour growth and regulating metastasis (the spreading of tumours throughout the body), which is the main killer ...

Breast CA nodal mets more common with certain mutations

July 25, 2013
(HealthDay)—Lymph node metastases are more common in breast cancers with mutations in a cellular signaling pathway associated with growth, according to a study published online July 24 in JAMA Surgery.

Potentially targetable signaling pathway generates slowly proliferating, chemo-resistant cancer cells

January 12, 2015
A signaling pathway responsible for the generation of slowly proliferating cancer cells, which are hard to eradicate with current treatments and thought to be a cause of subsequent disease relapse, has been reported in a ...

Recommended for you

Major study of genetics of breast cancer provides clues to mechanisms behind the disease

October 23, 2017
Seventy-two new genetic variants that contribute to the risk of developing breast cancer have been identified by a major international collaboration involving hundreds of researchers worldwide.

Proton therapy lowers treatment side effects in pediatric head and neck cancer patients

October 23, 2017
Pediatric patients with head and neck cancer can be treated with proton beam therapy (PBT) instead of traditional photon radiation, and it will result in similar outcomes with less impact on quality of life. Researchers from ...

New study shows how cells can be led down non-cancer path

October 23, 2017
As cells with a propensity for cancer break down food for energy, they reach a fork in the road: They can either continue energy production as healthy cells, or shift to the energy production profile of cancer cells. In a ...

Microbiologists contribute to possible new anti-TB treatment path

October 23, 2017
As part of the long effort to improve treatment of tuberculosis (TB), microbiologists led by Yasu Morita at the University of Massachusetts Amherst report that they have for the first time characterized a protein involved ...

Big Data shows how cancer interacts with its surroundings

October 23, 2017
By combining data from sources that at first seemed to be incompatible, UC San Francisco researchers have identified a molecular signature in tissue adjacent to tumors in eight of the most common cancers that suggests they ...

Symptom burden may increase hospital length of stay, readmission risk in advanced cancer

October 23, 2017
Hospitalized patients with advanced cancer who report more intense and numerous physical and psychological symptoms appear to be at risk for longer hospital stays and unplanned hospital readmissions. The report from a Massachusetts ...

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.