2. Academic Validation
  3. USP36 facilitates esophageal squamous carcinoma progression via stabilizing YAP

USP36 facilitates esophageal squamous carcinoma progression via stabilizing YAP

  • Cell Death Dis. 2022 Dec 5;13(12):1021. doi: 10.1038/s41419-022-05474-5.
Wenhao Zhang 1,  Junwen Luo 1,  Zhaohua Xiao 1,  Yifeng Zang 2,  Xin Li 3,  Yougjia Zhou 1,  Jie Zhou 1,  Zhongxian Tian 1 4,  Jian Zhu 5,  Xiaogang Zhao 6 7
Affiliations

Affiliations

  • 1 Department of Thoracic Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Shandong Province, People's Republic of China.
  • 2 Department of General Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Shandong Province, People's Republic of China.
  • 3 Xinxiang Key Laboratory of Tumor Migration and Invasion Precision Medicine, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, 453003, Henan Province, People's Republic of China.
  • 4 Key Laboratory of Thoracic Cancer in Universities of Shandong, Shandong University, Shandong Province, People's Republic of China.
  • 5 Department of General Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Shandong Province, People's Republic of China. zhujian1204@163.com.
  • 6 Department of Thoracic Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Shandong Province, People's Republic of China. zhaoxiaogang@sdu.edu.cn.
  • 7 Key Laboratory of Thoracic Cancer in Universities of Shandong, Shandong University, Shandong Province, People's Republic of China. zhaoxiaogang@sdu.edu.cn.
PMID: 36470870 DOI: 10.1038/s41419-022-05474-5
Abstract

Esophageal squamous carcinoma (ESCC) is the major subtype of esophageal Cancer in China, accounting for 90% of cases. Recent studies revealed that abnormalities in the Hippo/YAP axis are pervasive in ESCC and are recognized as the important driver of ESCC progression. Since the activity of Hippo signaling is controlled by phosphorylation cascade, it is a mystery why the major effector YAP is still over-activated when the cascade is inhibited. Several studies suggested that in addition to phosphorylation, Other protein modifications such as ubiquitination also play important roles in manipulating Hippo/YAP signaling activity. Since YAP protein stability is controlled via an appropriate balance between E3 ubiquitin ligases and deubiquitinases, we performed Deubiquitinase siRNA screening and identified USP36 as a Deubiquitinase significantly related to Hippo/YAP signaling activity and ESCC progression. USP36 expression was elevated in ESCC samples and correlated with poor differentiation. USP36 expression was correlated with YAP protein levels in ESCC samples. Molecular studies demonstrated that USP36 associated with the YAP protein and enhanced YAP protein stability by blocking the K48-linked polyubiquitination of YAP. In conclusion, our study revealed a novel Deubiquitinase in regulating Hippo signaling in ESCC, which could be an encouraging drug target for Hippo-driven ESCC.

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