Dissertations, Theses, and Capstone Projects

Date of Degree

9-2025

Document Type

Doctoral Dissertation

Degree Name

Doctor of Philosophy

Program

Biology

Advisor

Columba de la Parra

Committee Members

Moira Sauane

Anjana Saxena

Rodrigo Lacruz

Evgeny Pavlov

Subject Categories

Cancer Biology | Cell Biology

Keywords

cancer metabolism, mitochondria, calcium signaling, alternative translation, translation control

Abstract

Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer with a higher propensity for metastasis and poor patient prognosis. In order to withstand persistent oncogenic stress, TNBC cells adapt by reprogramming their metabolism and remodeling their proteome through translational control. These adaptations become particularly important under oxidative stress when canonical mRNA translation is suppressed. Despite this suppression in global translation, a subset of mRNAs will continue to be selectively translated through alternative mechanisms. One such mechanism is mediated by Death-Associated Protein 5 (DAP5), also known as NAT1, eIF4G2, p97, a ubiquitously expressed translation initiation factor that supports the selective translation of ~20-30% mRNAs that are critical for cell survival, migration, and metabolism. Elevated expression of DAP5 is correlated with poor survival and metastasis in TNBC patients. Currently, the role of selective translation initiation in the metabolic reprogramming of cancer remains largely unexplored. Here we demonstrate how DAP5 shapes key features of metabolic reprogramming and maintains a selective translatome under oxidative stress in TNBC. Collectively, these findings establish a novel framework for understanding how alternative mRNA translation supports metabolic reprogramming and adaptive survival in aggressive cancers.

Download

This work is embargoed and will be available for download on Thursday, April 30, 2026

Share

COinS