Dissertation Defense: Mechanisms of Intercellular Communication During Breast Cancer Progression Through Metastasis
Dissertation Defense: Mechanisms of Intercellular Communication During Breast Cancer Progression Through Metastasis
Christina Wheeler
Graduate Student, Translational Biology, Medicine, and Health
Graduate Research Assistant, Lamouille Lab, Fralin Biomedical Research Institute at VTC
April 11, 2024, at 10 a.m.
Room R3012, 2 Riverside Circle, Fralin Biomedical Research Institute at VTC, Roanoke, Virginia
About this Dissertation
Breast cancer is the second leading cause of cancer-related death in women worldwide. Despite more frequent and efficient screening measures, subtype-specific treatments, and overall improved patient outcomes, metastasis remains difficult to treat and accounts for 90% of breast cancer patient deaths. While the role of intercellular communication in metastasis, either among cancer cells, or between cancer cells and the tumor microenvironment is well established, additional research on specific molecular and cellular mechanisms underlying these interactions is necessary to develop novel therapeutic strategies. One mechanism that facilitates metastasis is epithelial-mesenchymal transition (EMT), which can be induced in cancer cells following the secretion of growth factors by tumor-associated macrophages (TAMs). During EMT, epithelial cells lose their cell-cell junctions, resulting in an alteration of intercellular communication. One of the junctions lost during EMT is gap junctions composed of connexin43 (Cx43), however, this is paired with an increase in expression of cytoplasmic Cx43. To elucidate the role of cytoplasmic Cx43 during EMT and breast cancer metastasis, Wheeler and the Lamouille Lab utilize a Cx43 mutant that has reduced binding with microtubules. Her research, mentored by Samy Lamouille, demonstrates disruption of the interaction between Cx43 and microtubules decreases mesenchymal marker expression and cell migration in vitro during EMT, and reduces breast cancer metastasis to the lungs in vivo, identifying a novel non-junctional tumorigenic role for Cx43 in metastasis and a potential therapeutic target in the treatment of breast cancer.
More About the Candidate and Project
Education
Virginia Tech, Translational Biology, Medicine, and Health, Ph.D. Candidate
Grand Valley State University, B.S., Cell and Molecular Biology
Training
Graduate Research Assistant, Lamouille Lab, Fralin Biomedical Research Institute at VTC
Mentor
Samy Lamouille, Ph.D., Assistant Professor, Fralin Biomedical Research Institute at VTC
Committee Members
- Irving Coy Allen, Ph.D., Professor, Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine
- Daniela Cimini, Ph.D., Professor, Department of Biological Sciences, College of Science, Virginia Tech
- Scott Johnstone, Ph.D., Assistant Professor, Fralin Biomedical Research Institute at VTC
- James Smyth, Ph.D., Associate Professor, Fralin Biomedical Research Institute at VTC
Publications
Christina E. Wheeler, Stacie E. Deaver, Kenneth L. Young II, Kevin He, Michael Zeitz, James W. Smyth, Samy Lamouille. Connexin43 interaction with microtubules promotes epithelial-mesenchymal transition and breast cancer metastasis. (In Preparation)
Christina E. Wheeler, Samy Lamouille. Epithelial-mesenchymal transition and tumor-associated macrophage alliance in breast cancer progression through metastasis. (In preparation)
- Ray Gaskins Health Sciences Scholarship, Fralin Biomedical Research Institute at VTC