Tumor extracellular vesicle-mediated signaling activates ketolysis to fuel cancer cell growth and metastasis in liver cancer

Professor Yam, Judy Wai Ping   (Principal Investigator (PI))

Professor Wong Alice Sze Tsai   (Co-Investigator)

36

2021-01-01

2023-12-31

1195024

Tumor extracellular vesicle-mediated signaling activates ketolysis to fuel cancer cell growth and metastasis in liver cancer

extracellular vesicles, hepatocellular carcinoma, ketolysis, nidogen-1, tumor necrosis factor receptor

Gastroenterology/HepatobiliaryCancer

Biology and Medicine (M)

17119120

General Research Fund (GRF)

2020

Completed

1 To delineate the mechanism of how EV-NID1 induces TNFR1 secretion by the activated pulmonary fibroblasts in pre-metastatic niche formation. We propose to demonstrate how the induction of TNFR1 by EV-NID1 is mediated by NF-kB pathway. We will examine the level and activation of NF-kB, the binding of NF-kB to TNFR1 promoter and the activity of TNFR1 promoter in fibroblasts treated with EV-NID1. 2 To characterize the functional effect of TNFR1-upregulated OXCT2 in enhancing ketolysis in HCC cells. We aim to answer whether OXCT2 promotes HCC metastasis by fueling HCC cells with energy generated by enhanced ketolysis. We will assess the phenotypes, levels of ketone bodies and cellular ATP in HCC cells with suppressed and elevated OXCT2 level. 3 To evaluate the therapeutic efficacy of anti-NID1 antibody in the blockage of EV signaling as a therapeutic strategy in HCC metastasis. The neutralizing effect of anti-NID1 antibody will be tested in various in vivo models involving the use of metastatic HCC cell lines, patient-derived xenografts and immunocompetent mice.