CtBP modulates Snail-mediated tumor invasion in Drosophila

Chenxi Wu; Xiang Ding; Zhuojie Li; Yuanyuan Huang; Qian Xu; Rui Zou; Mingyang Zhao; Hong Chang; Chunhua Jiang; Xiaojin La; Gufa Lin; Wenzhe Li; Lei Xue

doi:10.1038/s41420-021-00516-x

CtBP modulates Snail-mediated tumor invasion in Drosophila

Cell Death Discov. 2021 Aug 4;7(1):202. doi: 10.1038/s41420-021-00516-x.

Authors

Chenxi Wu^#^{1

2}, Xiang Ding^#¹, Zhuojie Li¹, Yuanyuan Huang¹, Qian Xu³, Rui Zou¹, Mingyang Zhao¹, Hong Chang², Chunhua Jiang², Xiaojin La², Gufa Lin⁴, Wenzhe Li⁵, Lei Xue^{6

7}

Affiliations

¹ The First Rehabilitation Hospital of Shanghai, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai, 200092, China.
² College of Traditional Chinese Medicine, North China University of Science and Technology, 21 Bohai Road, Tangshan, 063210, China.
³ College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China.
⁴ Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
⁵ The First Rehabilitation Hospital of Shanghai, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai, 200092, China. lwz@tongji.edu.cn.
⁶ The First Rehabilitation Hospital of Shanghai, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai, 200092, China. lei.xue@tongji.edu.cn.
⁷ Zhuhai Interventional Medical Center, Zhuhai Precision Medical Center, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Zhuhai, Guangdong, 51900, China. lei.xue@tongji.edu.cn.

^# Contributed equally.

Abstract

Cancer is one of the most fatal diseases that threaten human health, whereas more than 90% mortality of cancer patients is caused by tumor metastasis, rather than the growth of primary tumors. Thus, how to effectively control or even reverse the migration of tumor cells is of great significance for cancer therapy. CtBP, a transcriptional cofactor displaying high expression in a variety of human cancers, has become one of the main targets for cancer prediction, diagnosis, and treatment. The roles of CtBP in promoting tumorigenesis have been well studied in vitro, mostly based on gain-of-function, while its physiological functions in tumor invasion and the underlying mechanism remain largely elusive. Snail (Sna) is a well-known transcription factor involved in epithelial-to-mesenchymal transition (EMT) and tumor invasion, yet the mechanism that regulates Sna activity has not been fully understood. Using Drosophila as a model organism, we found that depletion of CtBP or snail (sna) suppressed Ras^V12/lgl^-/--triggered tumor growth and invasion, and disrupted cell polarity-induced invasive cell migration. In addition, loss of CtBP inhibits Ras^V12/Sna-induced tumor invasion and Sna-mediated invasive cell migration. Furthermore, both CtBP and Sna are physiologically required for developmental cell migration during thorax closure. Finally, Sna activates the JNK signaling and promotes JNK-dependent cell invasion. Given that CtBP physically interacts with Sna, our data suggest that CtBP and Sna may form a transcriptional complex that regulates JNK-dependent tumor invasion and cell migration in vivo.

Abstract

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