Endosome-mitochondria interactions in breast cancer cells

ABSTRACT
We propose that early endosomes function as a nexus between mitochondria and plasma membrane to
regulate a wide variety of cellular processes including receptor-mediated endosomal trafficking, signaling and
iron homeostasis. Determining how endosomal alterations on a subcellular level affect specific cancer-related
cellular processes, such as cell proliferation, migration and invasiveness is the focus of this research proposal.
Here, we will test the hypothesis that alterations in the early endosomal pathway can modify receptor-mediated
signaling as well as iron cellular homeostasis in a reciprocal manner to enhance the proliferative and survival
properties of cancer cells. We expect that the unravelling of the complex relationship between early
endosomes, mitochondria, iron and signaling and cancer progression will provide new tools for cancer therapy
and diagnosis. However, current approaches that investigate subcellular cancer cell biology of early
endosomal pathway on human breast cancer cells grown in 2D culture are not adequate to fully understand
how early endosomes can be re-programmed to support and enhance cancer cell proliferation, survival,
migration and/or invasiveness. Since 3D growth has been shown to affect organelle morphology, the analysis
of the morphology and function of organelles in 3D tumor systems is the new frontier of cancer cell biology.
Here, we will tackle this challenge by studying early endosomes, a complex and dynamic organelle, and their
interaction with mitochondria, in a comparative manner across 2D-culture cancer cell lines, 3D breast tumor
systems and human tumor frozen tissue sections. In summary, to advance our basic understanding of breast
cancer cell biology on a subcellular level, we will investigate the role of the morphology and function of early
endosomes and their interaction with mitochondria on the regulation of iron homeostasis and receptor-
mediated signaling pathways in 3D breast tumor systems.

Grant Number: 5R01CA233188-05
NIH Institute/Center: NIH
Principal Investigator: Margarida Barroso