Molecule linked to late-stage breast cancer

CASE WESTERN (US) — The discovery of a molecule associated with more aggressive forms of breast cancer could point the way to potential cures.

Prior to this study, published online in the Journal of Clinical Investigation, the ribonucleic acid (RNA) molecule called miR-181a had never before been tied to breast cancer metastasis—but when scientists found elevated levels of the molecule in late-stage breast cancer tissues, they tested an inhibitor in mouse models. The approach not only prevented metastasis, but also extended the animals’ lives.


“Overall, these findings reinforce our belief that the discovery of miR-181 will become a strong predictive biomarker for breast cancer metastasis, and that the high expression of miR-181 in tumor tissues will pave the way for the development of targeted therapies, better prognosis and increased patient survival,” says lead researcher William Schiemann, associate professor of general medical sciences (oncology) at Case Western Reserve University School of Medicine and a member of the Case Comprehensive Cancer Center.

As breast-cancer tumors spread, they become less responsive to chemotherapy.

Generating a cell-based system to replicate such changes enabled the research team to establish the molecule’s effect on breast cancer metastasis. The team also linked high levels of miR-181 with decreased levels of a protein molecule called Bim, which kills cancer cells during chemotherapy. The combination of low Bim levels and elevated miR-181a levels allowed the breast cancers to metastasize and resist chemotherapy.

“The identification of an RNA that regulates cell death may offer a natural molecule that can resensitize metastatic breast cancers to chemotherapy,” Schiemann says.

The research was supported in part by the National Institutes of Health, the Komen Foundation, and the University of Colorado Cancer Center Breast Program Gift Fund.

Source: Case Western Reserve University