Mitochondria as Drivers of Breast Tumor-initiating Cells – UROP Spring Symposium 2023

Mitochondria as Drivers of Breast Tumor-initiating Cells

Lillian Walton

Lillian Walton photo

Pronouns: She/ her

Research Mentor(s): Brock Humphries
Research Mentor School/College/Department: Department of Radiology / Medicine
Program: UROPF
Session: Session 1 (9:00am – 9:50am)
Authors: Lillian Walton, Anne Zhang, Brock Humphries

Abstract

Breast cancer is a complex disease that can be classified into three different subtypes. Of the subtypes, triple-negative breast cancer (TNBC), is considered the most aggressive because of its high levels of clinical heterogeneity and poor response to therapy. This subtype lacks the clinically actionable receptors, including the estrogen and human epidermal growth factor receptor-2 (HER2) receptors, that make other types of breast cancer susceptible to targeted treatments. The goal of the Humphries lab is to understand what drives this heterogeneity and how to target it. Currently we are studying how mitochondrial morphology regulates triple-negative breast cancer heterogeneity. Mitochondria exist along a spectrum of morphologies, from fissioned to fused, with each morphology driving different cellular behaviors. Through various molecular biology techniques including cell culture, viral transduction, transfection, and molecular imaging we are able to introduce genes that promote mitochondrial morphologies and image resultant effects on characteristics that define TNBC aggressiveness and heterogeneity. We analyze our results with MATLAB and Excel, and perform statistical analyses using student’s t-test or one-way ANOVA. We hypothesize that mitochondrial fission, where mitochondria separate display a shorter and more fragmented morphology, inhibits TNBC recurrence and metastasis by limiting heterogeneity. Our preliminary results show that enforcing mitochondrial fission limits the expression of genes that define a stem-like phenotype, a characteristic underlying cellular heterogeneity. Our overall goal is to identify how mitochondrial fission limits cancer stemness which will provide novel actionable therapeutic targets for the treatment of TNBC, improving the quality of life for patients with triple negative breast cancer.

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