P18 - Social Behavior of Breast Cancer Stem Cell in Metastasis

Abstract

My early work demonstrated that Rb tumor suppressor prevent the chemotherapeutic agent cisplatin-induced ROS stress and cell death by maintaining ATP and NAD levels as well as PARP-1 activity. Rb and Trp53 have been shown by the Sawyers and Goodrich groups in limiting cancer lineage plasticity through inhibiting Sox2 and Ezh2 pathways. My laboratory has focused on identifying gene and microRNA regulators of breast cancer stem cells in driving chemoresistance and metastasis, such as miR-30c, miR-138, and miR-206. While miR-138 targets EZH2 in breast CSCs to promote differentiation and inhibit tumor invasion, both miR-30c and miR-206 target cytoskeleton genes such as TWF1 to inhibit cancer stemness, chemoresistance and metastasis. Recently, we have identified a new social behavior of CSCs in circulating tumor cell cluster formation which greatly enhanced lung colonization and polyclonal metastasis of breast cancer. CTC clusters were less frequently detected but more metastatic than single CTCs of triple negative breast cancer patients and representative patient-derived-xenograft (PDX) models. Using intravital multiphoton microscopic imaging, we found that clustered tumor cells in migration and circulation resulted from aggregation of individual tumor cells rather than collective migration and cohesive shedding.