Therapeutic Strategies to Disrupt Cx26-FAK-NANOG Complex to Attenuate Cancer Stem Cell Self-Renewal and Triple-Negative Breast Cancer Progression
Abstract
Triple-negative breast cancer is the most aggressive breast cancer subtype and is resistant to therapies. Our objective is to neutralize cancer stem cells, which are thought to underlie resistance to chemotherapeutics, as well as recurrence and metastasis. In parallel, we seek to minimize collateral damage to normal non-cancer cells. We identified that the protein connexin 26 (Cx26) is necessary and sufficient for the survival of cancer stem cells in triple-negative breast cancer models. While Cx26 was previously proposed to be a tumor suppressor, epidemiological studies suggest otherwise, as patients with high Cx26 had a poorer prognosis. Our studies indicate that Cx26 promotes cancer stem cell survival by forming a protein complex with the transcription factor NANOG, a master regulator of cancer stem cell function, and focal adhesion kinase in triple-negative breast cancer but not in other breast cancers. Our objective is to prevent this complex from forming and thereby inhibit cancer Autonomous robots and vehicles must occasionally recover from locomotion failure in loosely consolidated granularterrain. Recent mobility challenges led NASA Johnson Space Center to develop a prototype robotic lunar roverResource Prospector 15 (RP15) capable of wheeled, legged, and crawling behavior. To systematically understandthe terradynamic performance of such a device, we developed a scaled-down rover robot and studied its locomotionon slopes of dry and wet granular media. Addition of a cyclic-legged gait to the robots wheel spinning action changesthe robot dynamics from that of a wheeled vehicle to a locomotor paddling through frictional fluid. Granular dragforce measurements and modified resistive force theory facilitate modeling of such dynamics. A peculiar gait strategythat agitates and cyclically reflows grains under the robot stem cell survival and growth. We will develop a therapeutic strategy to target complex formation that will be tested in pre-clinical models.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2021
- Accession Number
- AD1145730
Entities
People
- Emily Esakov
- Justin Lathia
- Ofer Reizes