SHARPIN Inhibits Esophageal Squamous Cell Carcinoma Progression by Modulating Hippo Signaling.,Neoplasia

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SHARPIN Inhibits Esophageal Squamous Cell Carcinoma Progression by Modulating Hippo Signaling.
Neoplasia ( IF 6.3 ) Pub Date : 2019-12-26 , DOI: 10.1016/j.neo.2019.12.001
Aijia Zhang ₁ , Weilong Wang ₁ , Zhijun Chen ₂ , Dan Pang ₁ , Xiaofeng Zhou ₃ , Kui Lu ₁ , Jinghan Hou ₁ , Sujie Wang ₁ , Can Gao ₁ , Benjie Lv ₁ , Ziyi Yan ₃ , Zhen Chen ₃ , Jian Zhu ₄ , Lidong Wang ₅ , Ting Zhuang ₆ , Xiumin Li ₁

Affiliation

Department of Gastroenterology, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang 453003, Henan Province, PR China; Center for Cancer Research, Xinxiang Medical University, Xinxiang 453003, Henan Province, PR China; Xinxiang Key Laboratory for Molecular Therapy of Cancer, Xinxiang Medical University, Xinxiang 453003, Henan Province, PR China.
Thoracic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453003, Henan Province, PR China.
Center for Cancer Research, Xinxiang Medical University, Xinxiang 453003, Henan Province, PR China; Xinxiang Key Laboratory for Molecular Therapy of Cancer, Xinxiang Medical University, Xinxiang 453003, Henan Province, PR China.
Henan Key Laboratory of Immunology and Targeted Therapy, School of Laboratory Medicine, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, Henan Province, PR China; Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, PR China.
Henan Key Laboratory for Esophageal Cancer Research and State Key Laboratory for Esophageal Cancer Prevention & Treatment of The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China.
Henan Key Laboratory of Immunology and Targeted Therapy, School of Laboratory Medicine, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, Henan Province, PR China.

Esophageal cancer is one of the leading malignancies worldwide, while around sixty percent of newly diagnosed cases are in China. In recent years, genome-wide sequencing studies and cancer biology studies show that Hippo signaling functions a critical role in esophageal squamous cell carcinoma (ESCC) progression, which could be a promising therapeutic targets in ESCC treatment. However, the detailed mechanisms of Hippo signaling dys-regulation in ESCC remain not clear. Here we identify SHARPIN protein as an endogenous inhibitor for YAP protein. SHARPIN depletion significantly decreases cell migration and invasion capacity in ESCC, which effects could be rescued by further YAP depletion. Depletion SHARPIN increases YAP protein level and YAP/TEAD target genes, such as CTGF and CYR61 in ESCC. Immuno-precipitation assay shows that SHARPIN associates with YAP, promoting YAP degradation possibly via inducing YAP K48-dependent poly-ubiquitination. Our study reveals a novel post-translational mechanism in modulating Hippo signaling in ESCC. Overexpression or activation of SHARPIN could be a promising strategy to target Hippo signaling for ESCC patients.

更新日期：2019-12-27

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