GRP78 Mediates Radiation Resistance of a Stem Cell-like Subpopulation Within the MCF-7 Breast Cancer Cell Line

Emerging evidence indicates that breast cancer-initiating cells (CICs) are relatively resistant to radiotherapy; however, the critical mechanisms determining breast CIC resistance to radiation remain elusive. In the present study, a subpopulation of cells displaying characteristics generally attributed to stem cells was identified within the breast cancer cell line MCF-7. This subpopulation displays cancer stem cell features characterized by overexpression of embryonic stem cell markers, high tumorigenic potential following transplantation into BALB/c-nu mice, self-renewal capacity and resistance to ionizing radiation (IR). Moreover, glucose‑regulated protein 78KD (GRP78), which was found to play a crucial role in stem cell oncogenesis, was also shown to be overexpressed in this subpopulation. GRP78 is required for the cancer stem-like subpopulation cell resistance to IR, as knockdown of this gene augments the effects of IR, while overexpression of GRP78 increases the radiation resistance of the subpopulation to IR. These findings indicate that GRP78 acts as a potential therapeutic target aimed at tumor-generating subsets of breast cancer cells.