Maria Soledad Sosa, Ph.D., Assistant Professor of Pharmacological Sciences, and Oncological Sciences, at The Tisch Cancer Institute at Mount Sinai. In this video, she speaks about the Mount Sinai Researchers Discover How Early-Stage Breast Cancer Can Become a Silent Killer in Some Patients.
Mount Sinai researchers have found a previously unknown process by which non-malignant cells from early breast cancer tumors migrate to other organs before "turning on" and becoming metastatic breast cancer.
The researchers also demonstrated the ability of the transcription factor NR2F1, a protein that controls a gene's outward expression, to prevent pre-malignant cells from spreading, which could be a critical diagnostic tool for predicting relapse.
A small but considerable proportion of women with early-stage breast cancer never develop an invasive breast tumor, which is the predicted progression of metastatic breast cancer. Instead, they die when their pre-malignant lesion recurs only in other organs, turning them into an unanticipated, silent killer. The mechanism by which pre-malignant cancer cells acquire mobile and invasive properties that allow diffusion and colonization in other organs was not well understood prior to this work.
Researchers investigated how these pre-malignant cells spread using animal models and pre-malignant breast cancer cells from patients, 3D culturing, and high-resolution imaging. The researchers discovered that pre-malignant cells downregulated the levels of NR2F1, which aided in dissemination, while also upregulating PRRX1, a master regulator of the invasive phenotype.
The scientists discovered pre-malignant cells in patients' ductal carcinoma in situ tissues that exhibited both low levels of NR2F1 and high levels of PRRX1, classifying them as a distinct pre-malignant subpopulation with the potential to spread. The therapeutic importance of this inverse ratio between NR2F1 and PRRX1 must be determined in a greater number of human samples, as well as through follow-up investigations on overall survival and metastasis-free survival.