Angiomotin promotes the malignant potential of colon cancer cells by activating the YAP-ERK/PI3K-AKT signaling pathway

Zhang,Yan; Yuan,Jun; Zhang,Xinli; Yan,Futang; Huang,Minggang; Wang,Tao; Zheng,Xiao; Zhang,Ming

doi:10.3892/or.2016.5194

Angiomotin promotes the malignant potential of colon cancer cells by activating the YAP-ERK/PI3K-AKT signaling pathway

Authors:
- Yan Zhang
- Jun Yuan
- Xinli Zhang
- Futang Yan
- Minggang Huang
- Tao Wang
- Xiao Zheng
- Ming Zhang
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Affiliations: Department of Medical Imaging, The First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China, Department of Clinical Laboratory, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China, Radio Immunity Center, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China, CT Department, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China, Department of Radiology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China
Published online on: October 21, 2016 https://doi.org/10.3892/or.2016.5194
Pages: 3619-3626

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Abstract

Colorectal cancer (CRC) is a leading cause of cancer-related deaths with an increasing incidence in China. The aberrant expression of angiomotin (AMOT) has been confirmed in a variety of tumors and can interact with Yes-associated protein (YAP) to either promote or suppress the progression of cancer. Unfortunately, its role in CRC remains poorly elucidated. Herein, higher levels of AMOT were observed in CRC cell lines. Upregulation of AMOT in LoVo cells markedly increased cell proliferation and apoptotic resistance to 5-fluorouracil. Moreover, its increase also promoted cell invasion and migration. Simultaneously, AMOT silencing markedly attenuated the growth and metastatic potential of HCT116 cells. Notably, AMOT upregulation promoted the activity of YAP by decreasing the expression of phosphorylated YAP and YAP in the cytoplasm and increasing YAP levels in the nucleus. Further mechanistic analysis corroborated that transfection with YAP siRNA notably diminished cell growth, invasion and migration in the AMOT‑overexpressing LoVo cells. Additionally, upregulation of AMOT induced the activation of the ERK and AKT pathways by YAP expression, both associated with the development of CRC. Collectively, these results suggest that AMOT may function as an oncogene in the progression of CRC by activating the YAP-ERK/PI3K-AKT signaling pathway. Therefore, this study presents a promising therapeutic target for CRC.

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