Biology of Breast Cancer Spotlight

Cell Surface Enablers of Breast Cancer Metastasis

PI: Jeroen Roose, UC San Francisco

By analyzing metastatic breast cancer samples from the bone and brain, researchers have identified unique surface markers that distinguish actively growing cancer cells from dormant ones. What are the key cell surface markers linked to metastatic breast cancer metabolism, and how can a better understanding different "archetypes" of metastasis improve treatments? By analyzing single-cell RNA sequencing (scRNAseq) data, researchers identified two potential markers—TM4SF1 and SLC39A6—that seem to define distinct metastatic profiles. The study yielded insights in three key areas: 1) Defining metastatic archetypes in brain tumors using scRNAseq and CyTOF, expanding insights beyond breast cancer, 2) Identifying gene expression patterns in patientderived xenograft (PDX) mouse models of breast cancer, and 3) Optimizing SCENITH staining to analyze metabolism at a single-cell level. The study yielded a high-impact publication in the journel Cell and another manuscript analyzing 15 patient-derived breast cancer samples. Future studies aim to deepen these findings and explore therapeutic potential.

An activated stem cell signature as a biomarker to predict malignant progression of DCIS

PI: Jay Desgrosellier, University of California, San Diego

Ductal carcinoma in situ (DCIS) is the most commonly diagnosed pre-malignant lesion in the breast. Only about half of these cases will progress to invasive breast cancer, yet many women with DCIS needlessly undergo aggressive treatment. To better understand which cases of DCIS are likely to become invasive, researchers studied whether an activated stem cell signature will identify DCIS lesions that are likely to progress to invasive breast cancer, in hopes of reducing unnecessary treatment. One of their most exciting discoveries was a specific type of cancer cell marked by a protein called RSAD2 (also known as Viperin). These RSAD2+ cells have stem-like properties, respond to immune signals, and are found more often in invasive cancers than in DCIS. The team also found that these cells can attract immune cells that actually help tumors grow and push neighboring cancer cells toward a more aggressive state. These findings suggest that RSAD2+ cells may play a central role in the shift from non-invasive to invasive cancer. The study generated 5 publications, including a report in Frontiers in Cell and Developmental Biology.