Page 6 - I. Chemical biology and drug discovery

[I. Chemical biology and drug discovery-3]

Inhibition of fatty acid binding protein 4 ameliorates

impaired ciliogenesis in gastric cancer cells

Yooju Jung¹, Jae-Ho Cheong², Ho Jeong Kwon¹˙*

¹Chemical Genomics Global Research Laboratory, Department of Biotechnology, Yonsei University, Seoul 120-749,

Korea, ²Department of Surgery, Yonsei University, Seoul 107-11, Korea

Ciliogenesis is often restrained in some cancer cells leading to accelerate cancer phenotypes such as cell migration
and proliferation. From the investigation of primary cilia of 17 gastric cancer cells (GCs), we found that 4 GCs

generated a low level of primary cilia whereas most of cells did not form cilia at all. It was previously reported that

notch signaling regulates ciliogenesis and fatty acid binding protein 4 (FABP4) is linked to the up-regulation of
notch signal in cancer. To identify the role of FABP4 in ciliogenesis, FABP4 expression and its function were inhibited
by siFABP4 or FABP4 inhibitor (FABP4i) treatment. Notably, the proliferation and notch signaling of the cilia forming

GCs were effectively suppressed when FABP4 was inhibited. In addition, the primary cilia in GCs were enriched twice
by inhibition of FABP4, suggesting the negative role of FABP4 in ciliogenesis of these cells. On the other hand, we

screened 893 small molecules that have structural similarity to FABP4i and identified hit compound that suppressed
cell growth and increased ciliogenesis with downregulation of activated notch1. Hit compound and FABP4i showed

tumor suppression effect in GC xenograft mouse model in vivo suggesting its potential as a new anti-cancer
therapeutic agent.