Gene Identified as Possible Target, Biomarker for Aggressive Breast Cancer

Transforming Growth Factor β (TGF-β) acts as a tumor suppressor, but it also promotes cancer progression within the tumor microenvironment--although how this happens is not entirely clear.

To learn more, California State University, Northridge biology professor Jonathan Kelber, PhD, and nine research students have identified a cancer “support wall” gene called PEAK1. They determined that PEAK1 is a possible target and maybe a biomarker identifying which patients would be good candidates for anti- TGF-β treatment. The results of their research were first published in the Public Library of Science (PLoS) One journal.¹

The research team evaluated the part that PEAK1 plays in the switching of TGF-β from a tumor suppressing to tumor promoting factor. They discovered that high PEAK1 expression causes TGF-β to lose its antiproliferative effects, enablling TGF-β to proliferate and also causing cell migration which can lead to tumor metastasis. According to the PloS journal article, PEAK1 mediates signaling cross talk between TGF-β receptors and integrin/Src/MAPK pathways, and that PEAK1 is an important molecular regulator of TGF-β-induced tumor progression and metastasis in breast cancer.

It appears that PEAK1 overexpression/upregulation cooperates with TGF-β to reduce breast cancer sensitivity to Src kinase inhibition.

In healthy human cells, the TGF-β protein keeps cell growth and placement from changing. But, in some types of breast cancer, the presence of TGF-β kicks off a process called epithelial-mesenchymal transition (EMT). EMT causes benign epithelial tumor cells to transform into malignant mesenchymal cells at an alarming speed.

Because PEAK1 is now identified as part of the tumor growth acceleration in breast cancer cells, patients who have high levels of the gene may be considered candidates for different cancer treatments that can alter PEAK1's behavior or at least slow it down, according to Dr. Kelber.

“[PEAK1 over-production] could indicate patients that have a poor prognosis and are better candidates for certain therapies that block the bad TGF-β effects,” Dr. Kelber said in a press release.²

References:

• Agajanian M, Campeau A, Hoover M. et al. PEAK1 Acts as a Molecular Switch to Regulate Context-Dependent TGFβ Responses in Breast Cancer. PLoS One, Aug 12;10(8):e0135748.
• California State University, Northridge Press Release. (2015). CSUN Biology Prof Paves Way for Future Breast Cancer Treatments.