About 1 in 8 U.S. women will develop breast cancer over the course of her lifetime, and in the year of 2014, breast cancer has claimed the lives of approximately 40,000 women and men in the United States. Although initial remission can be achieved with chemo-treatments, the worry and fear of treatment resistance, recurrence, and death still have a deep impact on many breast cancer patients. It is recognized that cancer stem cells (CSCs), a long-lived, self-perpetuating cell population that can infinitely give rise to the bulk of a tumor as the “seed” of the cancer, account for cancer initiation, progression, chemoresistance, and recurrence. To date, treatment strategies designed to eliminate the genesis of the cancer (CSC) still remain a significant challenge. This project aims to identify critical cell components and their working mechanisms that are used to sustain the stemness of breast CSCs, and the identified mechanism will further be therapeutically targeted to direct CSCs to a differentiated cell (non-stem cell) fate, allowing breast tumors to become terminally dormant and sensitive towards chemotherapy. Our goal is to eradicate breast cancer in the next 10 years, and with the common stemness properties of CSCs between many cancer types, we believe that the applications generated from our research will continuingly contribute to overcoming the therapeutic hurdles of a broad spectrum of cancers and significantly benefit the cancer patient and the survivor community for decades.