'Bridge' protein spurs deadliest stages of breast cancer

Led by professor Gen-Sheng Feng, Ph.D., and colleagues at Burnham and Royal Victoria Hospital in Montreal, Quebec, the study ranks among the first to more precisely define the cancer role for the protein known as Gab-2. These results, to be published in the journal Oncogene, have been made available to the worldwide medical research community by priority posting online at the journal’s website.

The protein has been of keen research interest for its role in breast cancer, but whether it controlled metastasis or initial tumor growth was unknown. Gab-2 is one of a group of proteins known as "scaffold" or "bridge" proteins, which provide a molecular intermediary to help cell signal proteins interact.

"Although Gab-2 is highly expressed in breast cancer, it is not essential for the development of cancer," said Feng. "We found that Gab-2 is, however, essential for metastasis, or the spread of cancer. Breast cancer victims can survive before metastasis, but their chances decrease significantly when the cancer cells have spread. If we can understand precisely how Gab-2 functions in metastasis, then we might be able use this knowledge to design treatments that would block the deadly metastasis."

Feng, who studies molecular signaling in embryonic stem cells and examines signaling pathways that are involved in obesity and diabetes, has studied the roles played by Gab-2 and its chemical cousin Gab-1, in various disorders. His fundamental analyses of cell signaling for Gab-2 led him to study the protein in cancer cells.

Feng and his colleagues began by examining Gab-2’s role in a pathway influenced by the cancer-causing oncogene Neu, which is implicated in nearly 30 percent of human breast cancers and associated with poor survival rates. While scientists have known that the Neu pathway drives cancer development and metastasis (and can be treated with the drug Herceptin with a certain degree of success), the molecular mechanisms that lead to breast cancer development and metastasis are not fully understood.

Feng worked with mice a special strain of mice which lacks the gene for Gab-2. The Gab-2 mutant mice were bred with two types of mice; one with an active gene that induced metastatic breast cancer tumors and another that grew breast cancer cells with low potential for metastasis.

The mutant mice showed minor effects from the initial growth of breast cancer cells, Feng and his team found, indicating that Gab-2 has little effect on inducing cancer cell growth. However, in the mice pre-disposed to metastatic breast caner, the lack of Gab-2 potently reduced metastasis rates, indicating that Gab-2 was necessary for metastasis, if not for initial tumor growth.

Since Gab-2 is a scaffold molecule and is possibly part of many signaling pathways, Feng’s group wanted to determine how it influences cancer cell growth. They studied pathways known as Akt and Erk, well-known parts of the Neu oncogene pathway, in the mice lacking Gab-2 and found that while levels of Akt signals were unaffected by Gab-2’s absence, Erk signals were significantly reduced.

"It appears that Akt and Erk pathways have distinctive roles in mammary tumors; initiation and growth for Akt and metastasis for Erk," said Feng. "We suspect that Gab-2 might promote mammary cell metastasis through Erk activation. This is a novel mechanism for breast cancer metastasis which makes Gab-2 a possible new target for the design of therapies for metastatic breast cancer."

Feng and his team are now looking at the other molecules that assist the scaffold protein Gab-2’s effects on breast cancer metastasis.

Source: Burnham Institute

Discovery of a mechanism that regulates cell movement
A study performed by researchers at the Institute for Research in Biomedicine (IRB Barcelona), in collaboration with researchers at the Instituto de Biología Molecular of the CSIC, reveal a mechanism that controls the movement of cells in a tissue by regulating cell adhesion. This same mechanism may be defective in diseases such as cancer and its metastasis, when tumour cells lose their adhesion to neighbouring cells and migrate through the organism. The results of this research have been published in this week's Nature Cell Biology.
Improving understanding of cell behavior in breast cancer
The invasion and spread of cancer cells to other parts of the body, known as metastasis, is a principal cause of death in patients diagnosed with breast cancer. Although patients with early stage, small, breast tumours have an excellent short term prognosis, more than 15 to 20 per cent of them will eventually develop distant metastases, and die from the disease. Vascular invasion — through lymphatic and blood vessels — is the major route for cancer spreading to regional lymph nodes and to the rest of the body.
Cellular decision on the computer
Scientists of the Division of Theoretical Bioinformatics at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg have simulated on the computer how cells decide whether or not to migrate. Using their results, the researchers were able to predict the molecular targets within a cell that have to be hit so that its behavior changes in a particular direction. This method may help to develop new treatments against cancer metastasis. The scientists have published their results in the latest issue of Molecular Systems Biology.
Prostate cancer vaccines more effective with hormone therapy
Among patients with castration-resistant prostate cancer, the addition of hormone therapy following vaccine treatment improved overall survival compared with either treatment alone or when the vaccine followed hormone treatment, according to recent data published in the July 15 Clinical Cancer Research, a journal of the American Association for Cancer Research.
Nanomaterials Key to New Strategies for Blocking Metastasis
A new treatment strategy using targeted nanoparticles to block metastasis with anti-cancer drugs leads to good results using significantly lower doses of toxic chemotherapy, with less collateral damage to surrounding tissue, according to a collaborative team of researchers at the Center of Nanotechnology for Treatment, Understanding, and Monitoring of Cancer at the University of California, San Diego. In designing this system, the investigators, led by David Cheresh, Ph.D., have identified what may become a generic method for using nanotechnology to target metastasis.
Researchers show antibody to breast cancer-secreted protein blocks metastasis
Scientists at the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia have made a key discovery about the mechanism of breast cancer metastasis, the process by which cancer spreads. Focusing on a gene dubbed "Dachshund," or DACH1, they are beginning to pinpoint new therapeutic targets to halt the spread of cancer.
'Smart bomb' nanoparticle strategy impacts metastasis
A new treatment strategy using molecular "smart bombs" to target metastasis with anti-cancer drugs leads to good results using significantly lower doses of toxic chemotherapy, with less collateral damage to surrounding tissue, according to a collaborative team of researchers at the University of California, San Diego.
Circulating tumor cells can reveal genetic signature of dangerous lung cancers
Massachusetts General Hospital (MGH) investigators have shown that an MGH-developed, microchip-based device that detects and analyzes tumor cells in the bloodstream can be used to determine the genetic signature of lung tumors, allowing identification of those appropriate for targeted treatment and monitoring genetic changes that occur during therapy. A pilot study of the device called the CTC-chip will appear in the July 24 New England Journal of Medicine and is receiving early online release.

'Bridge' protein spurs deadliest stages of breast cancer

Related stories:

News discussion: