Molecules called long non-coding RNAs (lncRNAs) have been implicated in breast cancer but exactly why they cause metastasis and tumour growth has been little understood, until now.
Scientists at The MD Anderson Cancer Center report that hedgehog, a unique cell signalling pathway known to contribute to many types of cancer, may be behind breast cancer metastasis. This molecular message service works with the lncRNA known as BCAR4 giving the genetic green light for tumour growth.
The study of BCAR4 and the hedgehog signalling 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.
When the hedgehog signalling pathway is activated abnormally by proteins known as chemokines, it allows increased expression of genes controlled by a transcription factor called GLI2. Transcription factors are proteins that activate other genes. The team found that BCAR4 is required for GLI2-controlled gene activation. This molecular liaison of BCAR4 via the hedgehog signalling pathway and GLI2 is the first understanding of the tie between hedgehog and BCAR4 in breast cancer.
This new information led the researchers to explore the potential for an emerging therapy known as locked nucleic acids (LNA) for breast cancer. Therapeutic targeting of lncRNAs has not been well documented for breast cancer. The current study aimed to determine their potential through use of an LNA-based therapy.
The group found that there was indeed a good outcome for LNAs in treating breast tumour spread when studied in mice, and human tissue and cell lines.
Therapeutic delivery of LNAs targeting BCAR4 strongly suppresses breast cancer metastasis. The team confirmed the link between BCAR4 and the hedgehog signalling pathway as a viable avenue for a new approach to treating aggressive breast cancers.