通过有丝分裂后中体的选择性自噬降解进行乳腺肿瘤消融
Breast Tumor Ablation by Selective Autophagic Degradation of Postmitotic Midbodies
关键词:乳腺癌;细胞分裂;细胞质;疾病
摘 要:Breast cancer develops from epithelial lesions in breast ducts and lobules that become invasive and can be metastatic. Breast cancer is a disease of uncontrolled cell division. Cell division normally creates two genetically identical daughter cells through severing of a cytoplasmic bridge that interconnects them. The midbody is an organelle involved in severing. Previously midbodies were thought to be lost from cells after division, but we show they can be retained. Here we show that MBs exhibit stem cell properties and are in breast cancer stem cells (Task 1). They are scaffolds for anchoring breast cancer oncogenes, tumor suppressors and breast cancer stem cell proteins. Increasing MB+ cells increases in vitro tumor potential ( Task 2). We activated a MB-degradation pathway that decreased MBs and tumorigenic properties of breast cancer cells (Task 3). Because MBs are in breast cancer stem cells, we believe this MB targeting strategy may be an innovative strategy for therapies focused on the most difficult of all tumors, those thought to be caused by cancer stem cells, namely recurrent, resistant and metastatic cancers.