Date of Completion

2024

Thesis Type

College of Arts and Science Honors

Department

Biology

First Advisor

Paula Deming, Ph.D.

Second Advisor

Alison Brody, Ph.D.

Keywords

lung cancer, breast cancer, metabolism, STK11, tumor suppressor gene, non-genomic signaling, hexosamine biosynthetic pathway

Abstract

Serine Threonine Kinase 11 (STK11) has been considered a tumor suppressor gene since its discovery. In lung cancer, loss of STK11 is associated with increased metastasis as well as metabolic reprogramming that causes a “glutamine addiction.” The work presented here aims to investigate how STK11 loss (ΔSTK11) alters metabolism and promotes metastasis in lung cancer. Our research found that, upon glutamine deprivation, ΔSTK11 cells are able to detach, remain alive, and re-establish in glutamine-rich media. The hexosamine biosynthetic pathway (HBP) is an offshoot of glycolysis and increased flux of this pathway can result in worsened cancer prognosis and an increased risk of metastasis. We found that these ΔSTK11 cells also have an increased HBP flux upon glutamine deprivation. Current work aims to establish whether enhanced HBP flux drives this pro-metastatic phenotype. In contrast to what has been observed in lung cancer, it has been reported that STK11 may actually have oncogenic properties depending on its cellular location in breast cancer. Another aspect of our research aimed to investigate the role of STK11 in promoting tumorigenesis in breast cancer. More specifically, how STK11 affects non-genomic signaling and metastatic potential in estrogen-receptor-positive (ER+) breast cancer cells. Our research found that estradiol stimulation activates the PI3K pathway in ER+ breast cancer cells, which is associated with effects on proliferation, metabolism, apoptosis, and more. Current work aims to generate ΔSTK11 cell lines to better investigate STK11’s effects on non-genomic signaling and metastatic potential in breast cancer cells. Overall, our results from this project provide important insight into the role of STK11 in both lung and breast cancers that can potentially aid in the future development of therapeutics.

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