Novel molecular pathway in aggressive breast cancer offers potential therapeutic targets

April 21, 2017
Breast cancer cell. Credit: University of Tsukuba

University of Tsukuba-led researchers identified a novel molecular mechanism involved in progression and metastasis in the most aggressive form of breast cancer. The gene MAFK is known to be induced by the TGF-β signaling pathway, which is involved in breast cancer development. The team reported that MAFK protein, in turn, induced cancerous behaviors in cells by switching on the breast cancer-associated gene GPNMB. MAFK thus represents a link between TGF-β signaling and GPNMB-induced breast cancer.

Breast is the most common type of cancer in women. It is divided into different types based on whether certain molecules, including receptors for hormones, are present. Triple-negative (TNBC), which lacks three key receptors, is the most aggressive form. TNBC frequently metastasizes to other organs and has poor prognosis. Understanding the molecular mechanisms underpinning TNBC is key to developing targeted molecular therapies for the condition.

An international research team led by the University of Tsukuba (Japan) has now identified a novel molecular mechanism contributing to progression and metastasis in TNBC. Musculoaponeurotic fibrosarcoma (MAF) oncogene family protein K (MAFK) is a protein involved in switching on specific target . The team previously identified MAFK as a gene that is itself switched on by a protein called TGF-β, which is known to be involved in TNBC development. The researchers confirmed MAFK as a functional link between TGF-β and TNBC. The findings were published in Science Signaling.

"The TGF-β signaling pathway is involved in TNBC progression and metastasis," corresponding author Mitsuyasu Kato says. "However, it's also involved in beneficial processes in healthy cells, and actually helps to suppress the early stages of tumor development. Identifying molecular processes downstream of the TGF-β pathway could offer specific targets for TNBC therapy to combat progression and metastasis without interfering with the beneficial effects of TGF-β signaling."

The team found higher levels of MAFK in TNBC cells than in other cancer cell types. A survey of patient data revealed that patients with higher MAFK gene activity had poorer prognosis. Moreover, when the team interfered with the production of MAFK in , the tumors the cells formed were smaller and metastasized to a lesser degree. Conversely, genetically engineering non-cancerous breast cells to make them produce MAFK caused them to behave like cancer cells.

There was already some evidence of MAFK promoting tumor development in other cancer types, but the underlying mechanism remained a mystery. By screening DNA, the team identified a gene, GPNMB, which is switched on by MAFK.

"We found that induction by MAFK of cancer-like behaviors in breast is dependent on GPNMB," lead author Yukari Okita says. "GPNMB is already known to be present at high levels in the most aggressive and lethal TNBC and to contribute to cancer development; our study identifies induction by MAFK as a missing link between the TGF-β pathway and GPNMB." Shedding light on this pathway therefore offers potential new therapeutic targets for patients with TNBC.

Explore further: Study identifies potential targets for treating triple negative breast cancer

More information: Yukari Okita et al. The transcription factor MAFK induces EMT and malignant progression of triple-negative breast cancer cells through its target GPNMB, Science Signaling (2017). DOI: 10.1126/scisignal.aak9397

Related Stories

Study identifies potential targets for treating triple negative breast cancer

August 29, 2016
No specific treatments are currently available for triple negative breast cancer (TNBC), a type of tumor that lacks the receptors targeted by many breast cancer therapies. Although many TNBC tumors lack two tumor suppressors, ...

Gene that inhibits tumor growth is shown to promote aggressive breast cancers

May 27, 2015
A*STAR researchers have shown that the RASAL2 gene, which is known to inhibit tumor growth in some breast cancers, actually advances tumor formation and metastasis in more aggressive forms of breast cancer and have suggested ...

Researchers identify novel treatment for aggressive form of breast cancer

May 23, 2016
A recent study by researchers at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine revealed that triple-negative breast cancer (TNBC), which has generally been unresponsive to hormone ...

A key to unlocking the mystery of triple negative breast cancer

October 24, 2016
A study conducted at the Research Institute of the McGill University Health Centre (RI-MUHC) suggests screening breast cancer patients for the prolactin receptor could improve the prognosis for patient and may help them avoid ...

Protein linked to invasive spread of triple-negative breast cancer may lead to targeted therapies

February 26, 2014
Triple-negative breast cancer (TNBC) is one of the most aggressive forms of the disease and affects almost one in seven of the 1.5 million women diagnosed with breast cancer worldwide each year. TNBC tumors are missing three ...

Discovery may help breast cancer treatment

November 7, 2014
Researchers led by Dr. Debra Auguste, associate professor, biomedical engineering, in the Grove School of Engineering at The City College of New York, have identified a molecule that could lead to developing treatment for ...

Recommended for you

Clear link between heavy vitamin B intake and lung cancer

August 22, 2017
New research suggests long-term, high-dose supplementation with vitamins B6 and B12—long touted by the vitamin industry for increasing energy and improving metabolism—is associated with a two- to four-fold increased lung ...

Study provides insight into link between two rare tumor syndromes

August 22, 2017
UCLA researchers have discovered that timing is everything when it comes to preventing a specific gene mutation in mice from developing rare and fast-growing cancerous tumors, which also affects young children. This mutation ...

Retaining one normal BRCA gene in breast, ovarian cancers influences patient survival

August 22, 2017
Determining which cancer patients are likely to be resistant to initial treatment is a major research effort of oncologists and laboratory scientists. Now, ascertaining who might fall into that category may become a little ...

Study identifies miR122 target sites in liver cancer and links a gene to patient survival

August 22, 2017
A new study of a molecule that regulates liver-cell metabolism and suppresses liver-cancer development shows that the molecule interacts with thousands of genes in liver cells, and that when levels of the molecule go down, ...

Zebrafish larvae could be used as 'avatars' to optimize personalized treatment of cancer

August 21, 2017
Portuguese scientists have for the first time shown that the larvae of a tiny fish could one day become the preferred model for predicting, in advance, the response of human malignant tumors to the various therapeutic drugs ...

Scientists discover vitamin C regulates stem cell function, curbs leukemia development

August 21, 2017
Not much is known about stem cell metabolism, but a new study from the Children's Medical Center Research Institute at UT Southwestern (CRI) has found that stem cells take up unusually high levels of vitamin C, which then ...

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.