Page 40 - The Hormel Institute 2024 Annual Report

40 | THE HORMEL INSTITUTE
// UNIVERSITY OF MINNESOTA
Why do cancers spread? Why would cancer invent a process that would ultimately cause the host to die? It
doesn’t make any sense—unless we consider that cancer doesn’t invent anything new, but hijacks normal processes that exist at some point during our development. If this is the case, then the process of metastasis—how cancer cells travel through the body—must be a normal physiological process that is corrupted by cancer.
This is the position my lab takes as we focus on addressing the elusive “why.”
I started my lab at HI in February 2024 and these first several months have laid the founda- tion from which my lab will investigate the many “whys”. I am grateful for the amazing support and infrastructure that I have been able to lever- age to launch my lab here.
The process of metastasis—how cancer cells travel throughout the body—has been investigat- ed for decades but, despite a wealth of studies, it is not well understood and remains poorly controlled clinically. Our research aims are to understand why some cancers metastasize in order to identify therapeutic vulnerabilities that could be leveraged to identify patients at risk early on and stop the spread of cancer.
Our lab found that if we genetically delete
(or ‘turn off’) an ion channel in cells known as
NALCN, this has no impact on how quickly the tumor grows. However, it has a huge impact on how quickly and aggressively cancer spreads throughout the body.
We identified that NALCN regulates the shedding of specific types of tumor cells called circulating tumor cells (CTCs), a known source of meta- static disease, into the peripheral bloodstream. When we examined human cancers that com- monly metastasize, we identified that deletion of NALCN or reduced expression in human breast cancer patient samples were associated with more aggressive subtypes (basal and HER2+),
a faster time to disease-relapse, and increased incidence of metastasis to intraperitoneal organs (mesentery, ovary, liver).
We will first focus on understanding the impact of NALCN loss of function mutations in normal mammary gland development and breast cancer metastasis by using tissues grown in a dish, called organoids, and breast cancer murine models.
Future expansion of this research program
will be possible through several new lines of research resulting from these studies, including our screening methods, which will identify addi- tional genetic mechanisms of metastasis. These studies hold promise to markedly advance our understanding of the metastatic process–the most important cause of cancer-related death.