Page 44 - Hormel Report 2023

Liang Liu, PhD
“Understanding the environmental origin of cancer and associated mechanisms will facilitate the development of targeted
cancer prevention strategies and therapies.”
Liang Liu
44 | THE HORMEL INSTITUTE // Chromatin and
Epigenetic Gene Regulation
ASSISTANT PROFESSOR
UNIVERSITY OF MINNESOTA
Research in my lab focuses on the cross- talk between genetic and epigenetic factors in regulating tissue homeostasis
and cancer development. We integrate genetics, epigenetics, and functional genomics studies to define the role of key cancer regulators in cancer development, and to identify actionable targets for cancer prevention and treatment.
Targeting the TXNIP-Dependent Oncogenic Pathways for Cancer Therapy.
Thioredoxin-interacting protein (TXNIP) plays
a pivotal role in metabolic regulation, but more recently, it has emerged as a potent tumor suppressor in various cancer models, including breast cancer. In this project, we seek to address two fundamental questions: 1) What are the key signaling pathways and cellular processes regulated by TXNIP that play a role in the pathogenesis of breast cancer? Furthermore,
2) Can these signaling pathways be targeted to eliminate breast cancer cells and halt the growth and progression of breast tumors as potential therapeutic strategies?
In preliminary studies, we have iden- tified two novel pathways through which TXNIP controls the growth and survival of breast cancer cells. One of these pathways hinges on its interaction with and the subsequent negative regulation of calpastatin (CAST), which, according to our initial findings, is a putative promot-
er of tumor growth. The other pathway involves the IL24-STAT3 signaling cascade. Based on these
preliminary results, we postulate that TXNIP exerts its inhibitory activity on breast cancer growth
and progression by interacting with and nega- tively regulating certain tumor-promoting factors, including CAST and STAT3 signaling. We will test this hypothesis through two independent studies that characterize TXNIP’s role as a tumor suppres- sor in breast cancer pathogenesis and assess the therapeutic potential of these newfound TXNIP- dependent pathways for treating breast cancer.
We have already identified and validated CAST as a novel interacting partner of TXNIP through co-immunoprecipitation and western blotting. Nevertheless, the precise role of CAST in cancer remains enigmatic. Knocking down CAST in MDA-MB-231 triple-negative breast cancer cells significantly reduced cell proliferation in vitro and inhibited tumor growth in xenograft in vivo models. We will next test the hypothesis that