WNT2-Mediated FZD2 Stabilization Regulates Esophageal Cancer Metastasis via STAT3 Signaling

Fu, Yufei1; Zheng, Qi2; Mao, Yingying3; Jiang, Xiyi4; Chen, Xin2; Liu, Pei1; Lv, Bin1; Huang, Tuxiong5,6; Yang, Jiao5,6; Cheng, Yongran4; Dai, Xiaoyi2; Dai, Chunyan1; Wang, Xi1; Yin, Yifei1; Song, Tengjiao7; Jin, Weiyang8; Zou, Chang9; Chen, Tianhui10,11; Fu, Li5,6; Chen, Zhe1

2020-07-16

10.3389/fonc.2020.01168

Frontiers in Oncology   影响因子和分区

2234-943X

Esophageal cancer micro environment factor WNT2 was critical in cancer metastasis. However, very little is known about WNT2 receptors and their role in the malignant progression of ESCC. The clinical significance and underlying molecular mechanisms of FZD2, one of the receptors of WNT2, was further investigated in ESCC. We found that FZD2 expression was positively correlated with WNT2 levels in clinical ESCC specimens through database analysis. Upregulated FZD2 expression was detected in 69% (69/100) of the primary ESCC cases examined, and increased FZD2 expression was significantly correlated with poor prognosis (P< 0.05). Mechanistically, FZD2 induced the migration and invasion of ESCC cells by regulating the FZD2/STAT3 signaling.In vivoxenograft experiments further revealed the metastasis-promoting role of FZD2 in ESCC. Moreover, we found that the WNT2 ligand could stabilize and phosphorylate the FZD2 receptor by attenuating FZD2 ubiquitination, leading to the activation of STAT3 signaling and the initiation of ESCC cell metastasis. Collectively, our data revealed that a novel non-canonical WNT2/FZD2/STAT3 signaling axis is critical for ESCC progression. Strategies targeting this specific signaling axis might be developed to treat patients with ESCC.

esophageal squamous cell carcinoma (ESCC) metastasis WNT2 FZD2 ubiquitination STAT3signaling

SCI

英语

其他

National Natural Science Foundation of China[81603340][81802887][81773945][81772957][81602917][81503297][81803775][81803776] ; National Key R&D program of China[2017YFA0503900][2017YFC0908200] ; Medical Health Science and Technology Project of Zhejiang Provincial Health Commission[2019RC228][2019RC229] ; Opening Project of Zhejiang Provincial First-rate Subject of the Zhejiang Chinese Medical University[ZXYJH2018004] ; Zhejiang Provincial Natural Science Foundation of China[LQ18H280005] ; Science and Technology Program of Guangdong Province in China[2017B030301016] ; Industry and Information Technology Foundation of Shenzhen[20180309100135860] ; Zhejiang Province-Ministry of Health[WKJ-ZJ-1714] ; State Bureau of Foreign Affairs[20173300013]

Oncology

Oncology

WOS:000556898400001

FRONTIERS MEDIA SA

Web of Science

1.Zhejiang Chinese Med Univ, Affiliated Hosp 1, Key Lab Digest Pathophysiol Zhejiang Prov, Hangzhou, Peoples R China
2.Zhejiang Univ, Dept Thorac & Cardiovasc Surg, Affiliated Hosp 1, Hangzhou, Peoples R China
3.Zhejiang Chinese Med Univ, Dept Epidemiol & Biostat, Hangzhou, Peoples R China
4.Zhejiang Acad Med Sci, Grp Mol Epidemiol & Canc Precis Prevent, Hangzhou, Peoples R China
5.Shenzhen Univ, Dept Pharmacol, Guangdong Prov Key Lab Reg Immun & Dis, Sch Med, Shenzhen, Peoples R China
6.Shenzhen Univ, Sch Med, Shenzhen Int Canc Ctr, Shenzhen, Peoples R China
7.Zhejiang Chinese Med Univ, Coll Life Sci, Hangzhou, Peoples R China
8.Hangzhou Normal Univ, Coll Life & Environm Sci, Hangzhou, Peoples R China
9.Jinan Univ, Clin Med Coll 2, Southern Univ Sci & Technol, Clin Med Res Ctr,Affiliated Hosp 1,Shenzhen Peopl, Shenzhen, Peoples R China
10.Univ Chinese Acad Sci, Zhejiang Canc Hosp, Dept Canc Prevent, Canc Hosp, Hangzhou, Peoples R China
11.Chinese Acad Sci, Inst Canc & Basic Med, Hangzhou, Peoples R China

Fu, Yufei,Zheng, Qi,Mao, Yingying,et al. WNT2-Mediated FZD2 Stabilization Regulates Esophageal Cancer Metastasis via STAT3 Signaling[J]. Frontiers in Oncology,2020,10.

Fu, Yufei.,Zheng, Qi.,Mao, Yingying.,Jiang, Xiyi.,Chen, Xin.,...&Chen, Zhe.(2020).WNT2-Mediated FZD2 Stabilization Regulates Esophageal Cancer Metastasis via STAT3 Signaling.Frontiers in Oncology,10.

Fu, Yufei,et al."WNT2-Mediated FZD2 Stabilization Regulates Esophageal Cancer Metastasis via STAT3 Signaling".Frontiers in Oncology 10(2020).