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 stem cell survival and growth. We will develop a therapeutic strategy to target complex formation that will be tested in preclinical models.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2022
- Accession Number
- AD1190686
Entities
People
- Justin Lathia
- Ofer Reizes