Abstract P5-07-04: Transition from a pre-malignant lesion to cancer does not require stemness of the cancer-originating cells in the lesion

Abstract

Abstract The precancerous lesion is the final step before malignancy, and is thus a key step to cancer prevention. Precancerous lesions are heterogeneous harboring distinct subsets of cells from stem cells to differentiated cells. Whether the stem cells or other subsets in these precancerous lesions are responsible for the eventual cancer remains unanswered. Here, we report that in the precancerous lesions of the MMTV-Wnt1 model of basal-like breast cancer, there exist the stem cell-enriched keratin 6a+ subset and more differentiated WAP+ cell subset. We demonstrate that both mutated Ras and B-Raf can robustly transform both cell subsets into cancer. These data suggest that multiple cell subsets in precancerous early lesions can evolve into cancer. This finding indicates that cancer prevention should target both self-renewing cells and other cell subsets in developing precancerous lesions in high-risk individuals. Citation Format: Bu W, Li Y. Transition from a pre-malignant lesion to cancer does not require stemness of the cancer-originating cells in the lesion [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-07-04.