Scientists at The University of Texas MD Anderson Cancer Center have discovered a signalling pathway responsible for breast cancer metastasis. The study, led by Liuqing Yang, Ph.D., assistant professor of molecular and cellular oncology, was published in this month’s issue of Cell. 

Molecules called long non-coding RNAs (lncRNAs) are known because of their role in metastasis and tumor growth. However, until now, the dimensions of that implication remained hidden under the complexity of the process.

The group of researchers reported that hedgehog, a unique cell signalling pathway known to contribute towards many types of cancer, may be the one responsible for breast cancer metastasis. This pathway is a type of molecular message service that works with a lncRNA known as BCAR4, and gives the genetic permission for tumors to grow.

“Our study of BCAR4 and the hedgehog signaling pathway has provided evidence for lncRNAs’ regulator roles in aggressive breast cancers progression. Emerging evidence has revealed lncRNAs as a new class of players in the development and progression of cancer”, Dr. Yang said in a MD Anderson news release.

Chemokines can abnormally activate the hedgehog signalling pathway. If such a situation occurs, an increased expression of the genes controlled by the transcription factor GLI2 is initiated. A transcription factor is a protein that has the power to activate other genes. The team found that BCAR4 is necessary for GLI2-controlled gene activation, evidencing the link between hedgehog and BCAR4 in breast cancer.

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In light of the new results, Dr. Yang decided to explore the potential of an emerging therapy for breast cancer: the locked nucleic acids (LNA). The outcomes are explained in the study, in which Dr. Yang explains, “Therapeutic targeting of lncRNAs has not been well documented for breast cancer (…) In our study, we aimed to determine their potential through use of an LNA-based therapy.”

The results, obtained through studies in mice, human tissue and cell lines, suggest that there is a strong potential for LNAs in the treatment of breast tumor spread.

“Therapeutic delivery of LNAs targeting BCAR4 strongly suppresses breast cancer metastasis (…) We confirmed the link between BCAR4 and the hedgehog signaling pathway as a viable avenue for a new approach to treating aggressive breast cancers,” Dr.  Yang explained.

This study was funded by the National Institutes of Health and the Cancer Prevention Research Institute of Texas.