Jieun Kim, PhD

Steatotic Liver Disease Fund for The Cure Postdoctoral Research Fellowship Award
$25,000 over one year

Cedars-Sinai Medical Center

Regulation and Role of CXCL12/CXCR4 Axis on Metastatic Microenvironmental Remodeling in Fatty Liver
Mentor: Ekihiro Seki, MD, PhD

Colorectal cancer stands as a global health concern, ranking third in both incidence and mortality rates. The substantial impact of colorectal cancer arises from its propensity to metastasize, frequently targeting the liver. Notably, up to 50% of colorectal cancer patients develop liver metastasis. Underlying liver conditions, such as fatty liver and metabolic dysfunction-associated steatotic liver disease (MASLD), significantly elevate the risk of liver metastasis from primary colorectal cancer. However, the detailed mechanisms behind this association remain unclear. This research aims to untangle the complex relationship between fatty liver and colorectal cancer liver metastasis. Colorectal cancer patients with pre-existing fatty liver face elevated metastasis risk. I hypothesize that fatty liver creates a favorable tumor microenvironment enticing cancer cells and supporting their growth in the liver. We recently found that fatty liver releases extracellular vesicles to promote liver metastasis. However, further studies are needed to fully understand the underlying mechanism. Firstly, this project will explore how fatty liver attracts colorectal cancer cells to the liver, a crucial step in the metastatic cascade. Secondly, this project will examine how fatty liver amplifies oncogenic signaling pathways during liver metastases, fostering cancer cell survival and growth. These processes also affect the liver's metastatic microenvironment, priming immunosuppressive and extracellular matrix-rich environment, and finally leading to anti-cancer therapy resistance. By comparing metastatic tumor growth in normal conditions and with fatty liver, I aim to uncover new insights and potential intervention points. Ultimately, I seek to interrupt the signals attracting cancer cells to the liver and create an environment where they struggle to thrive, which offers innovative strategies for treating or preventing colorectal cancer liver metastasis in patients having fatty liver.