A prickly pathway

The hedgehog cell signaling pathway, known to contribute to many cancers, may also be behind breast cancer metastasis. MD Anderson scientists have found the molecular message service works with the long non-coding RNA (lncRNA) known as BCAR4 to give the genetic green light for tumor growth.

When proteins called chemokines abnormally activate the hedgehog signaling pathway, increased gene expression occurs, controlled by a transcription factor (proteins that activate other genes) called GLI2. Yang’s team found that BCAR4 is required for GLI2-controlled gene activation, marking the first understanding of the tie between hedgehog and BCAR4 in breast cancer.

Next, Yang explored using locked nucleic acids (LNAs) for treating breast cancers spread in the cell lines of mice and human tissue.

“Therapeutic delivery of LNAs targeting BCAR4 strongly suppresses breast cancer metastasis,” says Liuqing Yang, Ph.D., assistant professor in Molecular and Cellular Oncology. “We confirmed the link between BCAR4 and the hedgehog signaling pathway as a viable avenue for a new approach to treating aggressive breast cancers.”

The study, published in the journal Cell, was funded by the National Institutes of Health and the Cancer Prevention Research Institute of Texas.