Study Reveals Potential Therapy Targets for Triple-Negative Breast Cancer

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Liuqing Yang, PhD

A multi-institutional international investigation led by scientists at The University of Texas MD Anderson Cancer Center, Houston, has revealed new information about how molecules called long noncoding RNAs (lncRNA) interact with HIF-1, a signaling pathway that is overexpressed in many cancers. HIF-1 has been shown to regulate breast cancer ­progression.

Need for Biomarkers and Therapeutic Targets

The team’s findings, published by Lin et al in Nature Cell Biology,1 explored the role of HIF-1 in triple-negative breast cancer. The study analyzed data from The Cancer Genome Atlas, a research program supported by the National Cancer Institute and National Human Genome Research Institute within the National Institutes of Health that is looking at genomic changes in more than 20 different types of cancer.

“Triple-negative breast cancer continues to be a severe health problem, demanding the consideration of emerging long noncoding RNAs as biomarkers and therapeutic targets in combating this disease,” said ­Liuqing Yang, PhD, Assistant Professor in the Department of Molecular & Cellular Oncology.

Dr. Yang and coauthor Chunru Lin, PhD, confirmed four sites for phosphorylation, impacting key cellular functions.

LINK-A Pathway

“Our study identified four previously unknown phosphorylation sites in a LINK-A–regulated signaling pathway,” said Dr. Lin. “These events predict a worse outcome in patients with triple-negative breast cancer, suggesting that the LINK-A pathway plays a critical role in this disease and may provide wide-ranging therapeutic treatment targets.”

The team identified an lncRNA known as LINK-A, which activates HIF-1 signaling in triple-negative breast cancer.

“Our study delineates an lncRNA-protein kinase module that regulates HIF-1,” said Dr. Yang.

“The LINK-A–dependent HIF-1 signalizing cascade and the consequent effects on cancer cells implicate LINK-A and LINK-A–interacting kinases and receptors as promising therapeutic targets for triple-negative breast cancer,” he concluded. ■


1. Lin A, Li C, Xing Z, et al: The LINK-A lncRNA activates normoxic HIFα signaling in triple-negative breast cancer. Nat Cell Biol. January 11, 2016 (early release online).