Page 5 - I. Chemical biology and drug discovery

Inhibition of fatty acid binding protein 4 ameliorates
impaired ciliogenesis in gastric cancer cells

1
Yooju Jung , Jae-Ho Cheong , and Ho Jeong Kwon 1
2
1 Chemical Genomics Global Research Laboratory, Department of Biotechnology, College of Life Science & Biotechnology,
Yonsei University, Seoul 03722, Korea
2 Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
BACKGROUND AIM
▶ FABP4 (Fatty Acid Binding Protein 4) in cancer ▶ Investigation on correlation between FABP4 and primary cilia in gastric
• FABP4 is known as a carrier protein for fatty acids in adipocyte. cancer
• Recently, FABP4 has been reported as a cancer related protein in different kindsof cancer. • Although FABP4 plays an important role in cancer cells, its mechanism still remains
•FABP4 contributes to poor prognosis in ovarian cancer and could be a target for therapeutic unclear in gastric cancer cell lines.
intervention for cancer . • Microarray assay on gastric cancer patients tissue indicated those who express lower
amounts of FABP4 presented higher survival rate.
▶ Primary cilia as a cell cycleregulator in cancer • Furthermore, Primary cilia has been recognized as a signaling center for tumorigenesis.
•Primary cilium assembly begins at the G0/G1 phase of the cell cycle and starts to disassemble • Accordingly, we hypothesize that there could be a correlation between FABP4 and
when cells re-enter the cell cycle. primary cilia in gastriccancer.
• Primary cilia is deficient in many cancer cells and their proliferation is upregulated. Restoring
primary cilia in cancersis one of the novel therapeuticapproach.

Methods
▶ ICC (Immunocytochemistry)
▶ TCGAanalysis
▶ In silico docking analysis
▶ Xenograft mouse model
RESULTS
Fig1. Investigation of primary cilia on 17 gastric cancer cell lines Fig4. Compound 2 (FTPPP) is identified as a hit compound

Fig2. A reciprocal correlation between FABP4 and gastric cancer

Fig5. FABP4 regulates primary cilia through NOTCH signaling

Fig3. Primary cilia is upregulated by FABP4i and siFABP4 Fig6. Inhibition of FABP4 shows anti-tumor effect on GC xenograft
treatment mouse model in vivo

CONCLUSION REFERENCES

◆ Primary cilia is deficient in most of gastric cancer cells than GES-1, a normal gastric cell. 1. Kshipra M. Gharpure et al., Nature comm, 2018
2. Siew Cheng Phua et al., Cell, 2017
◆ FABP4 is upregulated in primary cilia-positive gastric cancer cell lines 3. Dorte L Egeberg et al., Cilia, 2012
◆ GC patients with high level of FABP4 shows poor prognosis 4. Khan Na et al, Oncotarget, 2016
5. U Harjes et al., Oncogene, 2017
◆ Functional inhibition of FABP4 by small molecules and its knock-down can ameliorate Contact information
impaired ciliogenesis in gastric cancer cells through downregulation of NOTCH signaling
• Presenter: YoojuJung
◆ Inhibition of FABP4 shows anti-tumor effect in GC xenograft mouse model in vivo uzzu1226@yonsei.ac.kr
suggesting its potential as a new anti-cancer therapeutic agent * Correspondence: Ho Jeong Kwon
kwonhj@yonsei.ac.kr
This work was partly supported by grants from the National Research Foundation of Korea, funded by the Korean government (MSIP; 2015M3A9B6027818) and Brain Korea 21 Plus Project, Republic of Korea