Page 1 - D. Cancer biology

Understanding functional roles of FAM86A

in NF-κB mediated gastric tumorigenic responses

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Yo Han Hong , Jae Gwang Park , Han Gyung Kim , Nur Aziz , Long You , Chaoran Song , Wooram Choi , Jieun Oh and Jae Youl Cho 1
1 Integrative biotechnology, Sungkyunkwan University, Suwon 16419, Korea
2 Colorectal Cancer Branch, National Cancer Center, Goyang 10408, Korea
BACKGROUND AIM
Gastric cancer is the one of the most lethal and third In this study, we investigated functional roles of
cause of cancer related mortality. Gastric cancer is FAM86A on the gastric tumorigenic responses.
involved in various oncogenic signaling pathways.
FGFR1-PI3K-AKT-NF-κB signaling pathway affects the METHODS
expression of various genes that regulate tumorigenic
responses. These responses are known to be regulated Clinical impact of FAM86A was assessed in total 426
patients with gastric cancer. Immunoblot and realtime PCR
by post-translational modifications. Methylation as one of were used to detect FAM86A expression in cell lines and
the post-translational modifications change protein patient samples. QunatSeq 3’ mRNA-Seq was used to
structure, activity, and localization. FAM86A as a non- screen the target genes of FAM86A. Biological functions of
histone protein lysine methyltransferase has novelty and FAM86A were examined in vitro and in vivo.
conserved sequence in the various species. However, Immunoprecipitation and mass spectrometry were
biological functions of FAM86A remain unclear. conducted to identify the specific binding partners.
RESULTS
Here, we report the identification of the Figure 1. Clinicopathological Figure 2. Biological landscape of
FAM86A as a candidate biomarker in gastric significance of FAM86A in gastric FAM86A
cancer. FAM86A was overexpressed in human cancer
gastric cancer specimens and cell lines. Using
gastric cancer patient samples from Asia
Cancer Research Group (ACRG) database and
Ajou University Hospital, FAM86A
overexpression positively correlated with
clinicopathological characteristics of gastric
cancer such as lymph vascular invasion and
Lauren intestinal type, and was independently
associated with poor survival. RNA sequencing
analysis revealed that knockdown of FAM86A Figure 4. Molecular mechanism of
in gastric cancer cells is accompanied by a Figure 3. Oncogenic function of FAM86A
decrease in the expression of angiogenesis, FAM86A in vitro and in vivo
metastasis and chemotaxis related genes,
including VEGF, IL-6 and MMP7. Results from
loss-of-function and gain-of-function
experiments suggested that knockdown of
FAM86A attenuated, while overexpression of
FAM86A enhanced, the invasion, migration and
colony forming ability of gastric cancer cells in
vitro and in vivo. Mechanistically, we found that
FGFR1-PI3K-AKT-NF-κB signal pathway and
its downstream effectors, such as MMP7,
VEGF and IL-6, were required for FAM86A
mediated tumor metastasis of gastric cancer.
FAM86A interacted with FGFR1 and
subsequently activated the FGFR1-PI3K-AKT- Figure 5. Clinical relevance
NF-κB signaling pathway by methylation between FAM86A and FGFR1
dependent manner. We also found that protein
expression of FAM86A was correlated with
activation of FGFR1 in human gastric cancer
specimens.
CONCLUSION REFERENCES ACKNOWLEDGEMENTS

[1] HAMAMOTO, Ryuji; SALOURA, Vassiliki; NAKAMURA, This work was supported by National Research Foundation
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Science Research Program)
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