TY - JOUR
T1 - KIF23 activated Wnt/β-catenin signaling pathway through direct interaction with Amer1 in gastric cancer
AU - Liu, Yi
AU - Chen, Hui
AU - Dong, Ping
AU - Xie, Guohua
AU - Zhou, Yunlan
AU - Ma, Yanhui
AU - Yuan, Xiangliang
AU - Yang, Junyao
AU - Han, Li
AU - Chen, Lei
AU - Shen, Lisong
N1 - Funding Information:
We thank our colleagues in the Department of Laboratory Medicine for the helpful discussions and valuable assistance. Also, we thank the participating patients for the source of clinical samples. This work was supported by the National Natural Science Foundation of China (grant number 81903038, 81874152, 81072009, 81372641, 81402332, 81772525, 81903038) to L. Shen, H. Chen, X. Yuan, Y. Liu and the Shanghai Sailing Program (grant number 19YF1432700) to Y. Liu.
Publisher Copyright:
© Liu et al.
PY - 2020/5/15
Y1 - 2020/5/15
N2 - Increased expression of the kinesin family member 23 (KIF23) has been verified in gastric cancer (GC) and its upregulation contributes to cell proliferation. Even though, the role of KIF23 has not been fully elucidated in GC, and the mechanisms of KIF23 as an oncogene remain unknown. To further identify its potential role in GC, we analyzed gene expression data from GC patients in GEO and TCGA datasets. KIF23 was upregulated in GC, and increased expression of KIF23 correlated with poor prognosis. Importantly, KIF23 inhibition not only suppressed GC cell proliferation, tumorigenesis, but also migration and invasion, and arrested the cell cycle in the G2/M phase. Mechanistic investigations confirmed that KIF23 activated the Wnt/β-catenin signaling pathway by directly interacting with APC membrane recruitment 1 (Amer1). Furthermore, KIF23 exhibited competitive binding with Amer1 to block the association of Amer1 with adenomatous polyposis coli (APC), thus relocating Amer1 from the membrane and cytoplasm to the nucleus and attenuating the ability of Amer1 to negatively regulate Wnt/β-catenin signaling, resulting in activation of this signaling pathway. Collectively, our findings demonstrated that KIF23 promoted GC cell proliferation by directly interacting with Amer1 and activating the Wnt/β-catenin signaling pathway.
AB - Increased expression of the kinesin family member 23 (KIF23) has been verified in gastric cancer (GC) and its upregulation contributes to cell proliferation. Even though, the role of KIF23 has not been fully elucidated in GC, and the mechanisms of KIF23 as an oncogene remain unknown. To further identify its potential role in GC, we analyzed gene expression data from GC patients in GEO and TCGA datasets. KIF23 was upregulated in GC, and increased expression of KIF23 correlated with poor prognosis. Importantly, KIF23 inhibition not only suppressed GC cell proliferation, tumorigenesis, but also migration and invasion, and arrested the cell cycle in the G2/M phase. Mechanistic investigations confirmed that KIF23 activated the Wnt/β-catenin signaling pathway by directly interacting with APC membrane recruitment 1 (Amer1). Furthermore, KIF23 exhibited competitive binding with Amer1 to block the association of Amer1 with adenomatous polyposis coli (APC), thus relocating Amer1 from the membrane and cytoplasm to the nucleus and attenuating the ability of Amer1 to negatively regulate Wnt/β-catenin signaling, resulting in activation of this signaling pathway. Collectively, our findings demonstrated that KIF23 promoted GC cell proliferation by directly interacting with Amer1 and activating the Wnt/β-catenin signaling pathway.
KW - Amer1
KW - Cell growth
KW - Gastric cancer
KW - KIF23
KW - Wnt/ß-catenin signaling pathway
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U2 - 10.18632/aging.103146
DO - 10.18632/aging.103146
M3 - Article
C2 - 32365332
AN - SCOPUS:85085196196
SN - 1945-4589
VL - 12
SP - 8372
EP - 8396
JO - Aging
JF - Aging
IS - 9
ER -