机构：[1]Department of General Surgery, The Second Affiliated Hospital of Soochow University, No.1055 Sanxiang Road, Suzhou 215004, China[2]School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China[3]State Key Lab of Radiation Medicine and Protection, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China.
出处：
ISSN：
摘要：
Ankyrin repeat and KH domain containing 1 (ANKHD1) is a protein with multiple ankyrin repeat domains and a single KH domain, and it is encoded by the ANKHD1 gene in humans. ANKHD1 has been reported to be highly expressed in various cancer tissues, and it is involved in cancer progression, including proliferation and invasion. However, its functional roles in colorectal cancer (CRC) remain unclear. In our study, we first found that high expression of ANKHD1 in CRC tumor tissue was associated with tumor infiltration depth (P=0.03). ANKHD1 was highly expressed in HCT116 and SW480 cells. Downregulation of ANKHD1 inhibited CRC cell proliferation, migration and invasion both in vitro and in vivo. ANKHD1 silencing inhibited the expression of MMP2, MMP9, the mesenchymal marker vimentin, and the epithelial-to-mesenchymal transition (EMT) transcription factors Snail and ZEB1, while increasing the expression of the epithelial marker E-cadherin. As a cofactor of YAP1 in the Hippo signaling pathway, ANKHD1 silencing reduced the expression and increased the phosphorylation of YAP1. Moreover, the phosphorylation of AKT was inhibited when ANKHD1 was knocked down. The mechanism study revealed that the effect of ANKHD1 might be associated with the expression of YAP1 and that AKT signaling and EMT played crucial roles in this process. Overexpression of YAP1 reversed the effect of ANKHD1 silencing on CRC cell proliferation, migration and invasion. In conclusion, these findings suggest that ANKHD1 might act as a novel regulator that promotes CRC cell proliferation, migration and invasion by activating EMT via YAP1.
基金：
This work was supported by the National
Natural Science Foundation of China (No
81672970 and 81673100), the Suzhou Key
Medical Center (No LCZX201505), the project
of Suzhou Science and Technology Development
Plan (No SZS201618 and SS201753),
the Health and Family Planning Commission
Fund Project of Jiangsu Province (No CXTDA2017016),
the Second Affiliated Hospital of
Soochow University Preponderant Clinic Discipline
Group Project Funding, Graduate Student
Scientific Research Innovation Projects of
Jiangsu Province (No KYCX18_2534), and Key
Scientific Development Program of China (No
2016YFC0904702).
第一作者机构：[1]Department of General Surgery, The Second Affiliated Hospital of Soochow University, No.1055 Sanxiang Road, Suzhou 215004, China
共同第一作者：
通讯作者：
通讯机构：[*1]Department of General Surgery, The Second Affiliated Hospital of Soochow University, No. 1055 Sanxiang Road, Suzhou 214004, China.[*2]School of Radiation Medicine and Protection, Medical College of Soochow University, No. 199 Ren’ai Road, Suzhou 215123, China.
推荐引用方式(GB/T 7714)：
Ping’an Yao,Yecheng Li,Wenqi Shen,et al.ANKHD1 silencing suppresses the proliferation, migration and invasion of CRC cells by inhibiting YAP1-induced activation of EMT.[J].American journal of cancer research.2018,8(11):2311-2324.
APA：
Ping’an Yao,Yecheng Li,Wenqi Shen,Xiaohui Xu,Wei Zhu...&Chungen Xing.(2018).ANKHD1 silencing suppresses the proliferation, migration and invasion of CRC cells by inhibiting YAP1-induced activation of EMT..American journal of cancer research,8,(11)
MLA：
Ping’an Yao,et al."ANKHD1 silencing suppresses the proliferation, migration and invasion of CRC cells by inhibiting YAP1-induced activation of EMT.".American journal of cancer research 8..11(2018):2311-2324
