The full text of this item is not available at this time because the student has placed this item under an embargo for a period of time. The Libraries are not authorized to provide a copy of this work during the embargo period, even for Texas A&M users with NetID.
mTOR: A Mechanistic Target of Muscle and Cancer Crosstalk
MetadataShow full item record
In the United States, the number of colon and breast cancer cases that are attributed to physical inactivity lead the exercise-associated cases of heart disease and type II diabetes. For the millions of people in the United States burdened with breast cancer, there is a noted substantial risk reduction with increased physical activity. Previous research has investigated skeletal muscle’s endocrine-like potential on inflammation and cancer metabolism; however there is limited investigation into exercise-facilitated suppression of cancer’s major anabolic pathway, the mechanistic target of rapamycin (mTOR) pathway. While previous cancer research has established that mTOR’s activity is dysregulated in cancer, little is known about the impact of exercise on the regulation of anabolic/proliferative features of breast cancer cells, nor has exercise been evaluated as a mediator of muscle and cancer crosstalk. This project’s objective is to determine how exercise is affecting the biological regulation of tumorgenesis (a critical component of treatment innovation) via the mTOR pathway, and how that regulation is mediated by skeletal muscle contraction. While research efforts and analyses about the mTOR pathway have led to key insights into its regulation of apoptotic and autophagic signaling in cancer, these efforts do not capture the complete profile of mTOR control on cell growth and survival, nor address preliminary data indicating that cellular proliferation rates are significantly reduced in breast cancer cells treated with excretion factors arising from contracting skeletal muscle (“exercise”). The work presented here-in utilizes a research approach consisting of cell culture and animal models to investigate key mechanistic foundations that underlie the biological regulation of breast cancer in individuals who partake in exercise. Specifically, the MCF7 epithelial breast cancer cell line, a hemicorpus hind limb perfusion (HHLP) surgery, and pharmacological interventions allow for evaluation of skeletal muscle’s endocrine ability, global protein synthesis, signal transduction and gene expression. The investigators’ consideration of musclecancer crosstalk via exercise lays the foundation for future evaluation of muscle-derived biomolecules (ie. microRNA) as a potential crosstalk mediators. This project’s successful completion proposes key mechanistic foundations that underlie the biological regulation of breast cancer, contributing greatly to science’s efforts towards novel translational investigation of the beneficial relationship between muscle and cancer crosstalk. Establishing a casual role for exercise as primary cancer prevention would have major translational impact in cancer prevention and patient survivorship, with even a small reduction in incidence of cancer resulting in multi- billion dollar health care savings.
Goodenough, Chelsea Goodliffe (2019). mTOR: A Mechanistic Target of Muscle and Cancer Crosstalk. Doctoral dissertation, Texas A&M University. Available electronically from