Newly Discovered Molecular-Level Mechanism May Increase the Growth of Breast Cancer Cells
Researchers at VTT Technical Research Centre of Finland, the University of Turku, Finland, and the University of Oslo, Norway, have discovered a previously unknown molecular-level mechanism that may partly explain the increased growth of cancer cells. The study, published in the British Journal of Cancer by Winsel et al, showed that high levels of the microRNA (miRNA)-378a-5p molecule cause cell-division anomalies. This renders the number of chromosomes in cancer cells abnormal, which is known to promote growth and the spread of cancer.
In addition, the researchers discovered that elevated miRNA378a-5p levels in breast cancer patients correlate with the most aggressive forms of cancer. The objective is to develop new diagnostic methods for breast cancer on the basis of the research results.
Study Details
The objective of the research project led by Marko Kallio, PhD, MSc, Principal Scientist at VTT, was to identify novel microRNAs participating in the regulation of cell division among the over 1,000 microRNAs found in humans. The investigators found that elevated miR-378a-5p levels perturb mitotic fidelity, which is known to be one of the factors promoting the generation, growth, and spread of cancer.
The researchers also succeeded in discovering a molecule-level mechanism that can explain the observed chromosome changes caused by overexpression of miR-378a-5p; excess of this particular microRNA in cancer cells leads to significant suppression of Aurora B kinase, which is an essential protein needed for faithful cell division.
In addition, overexpression of miR-378a-5p was found to reduce the sensitivity of cancer cells to paclitaxel treatment and to activate certain cell surface receptors, which transmit signals regulating, for example, angiogenesis. The observation concerning activation of receptors is consistent with a Canadian study published earlier showing that overexpression of miR-378a-5p stimulates neovascularization in tumors.
Additional Findings
In addition to the new observations concerning pathogenesis of cancer and drug response of cancer cells, the Finnish-Norwegian study is also significant due to the research results obtained from the tumors of breast cancer patients. Elevated miR-378a-5p levels were detected particularly in the most aggressive grade 3 breast tumors, which are associated with poor patient outcomes. In the future, the research group will attempt to verify the results in a more extensive patient study, with the additional objective of developing new diagnostic methods based on the expression of microRNA molecules.
The results of the research project headed by Dr. Kallio give new perspectives on earlier microRNA studies, and reinforce the theory that cancer cells take advantage of microRNA molecules when striving to multiply and spread. In the case of the miR-378a-5p molecule, its overexpression in cancer tissue may stimulate angiogenesis in tumors, enhance the energy metabolism of cancer cells, reduce the sensitivity of cancer cells to paclitaxel therapy, and induce chromosome changes.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
