Int J Biol Sci 2020; 16(11):1917-1928. doi:10.7150/ijbs.44429

Research Paper

Septin4 promotes cell death in human colon cancer cells by interacting with BAX

Xin Zhao1*, Hao Feng2*, Yang Wang3, Yanmei Wu3, Qiqiang Guo1, Yanling Feng1, Mengtao Ma1, Wendong Guo1, Xiaoyu Song1, Ying Zhang4✉, Shuai Han5✉, Liu Cao1✉

1. Key Laboratory of Medical Cell Biology, Ministry of Education; Institute of Translational Medicine, Collegeof Medical Science, China Medical University; Liaoning Province, Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, Shenyang, Liaoning Province, China
2. Department of Ophthalmology, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
3. Panjin Liaohe Oilfield Gem Flower Hospital, Panjin, Liaoning Province, China
4. Department of Cardiology, the First Hospital of China Medical University, Shenyang, Liaoning, China.
5. Department of Neurosurgery, the First Hospital of China Medical University, Shenyang Liaoning Province, China
*These authors contributed equally to this work.

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Citation:
Zhao X, Feng H, Wang Y, Wu Y, Guo Q, Feng Y, Ma M, Guo W, Song X, Zhang Y, Han S, Cao L. Septin4 promotes cell death in human colon cancer cells by interacting with BAX. Int J Biol Sci 2020; 16(11):1917-1928. doi:10.7150/ijbs.44429. Available from http://www.ijbs.com/v16p1917.htm

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Abstract

Septin4 is a tumor suppressor protein that promotes cell programmed death in various cell types through specifically antagonizing XIAP (X linked inhibitor of apoptosis), little is known its other novel binding partner and role in colorectal cancer. In this study, we found that Septin4 significantly expressed lower in human colon cancer when compared to peri-tumor benign cells, and its low expression was significantly associated with worse prognostic outcomes. Furthermore, Septin4 participated in DOX-induced colon cancer cell death in vitro. Septin4-overexpressing colon cancer cells displayed augmented apoptotic cell death and ROS production. Additionally, Septin4-knockdown cells revealed a resistance of DOX-induced cell death and reduced ROS production. Importantly, we first identified that BAX is a novel Septin4 binding partner and the interaction is enhanced under DOX treatment. Finally, Septin4-knockdown promoted colon cells growth in vivo. These observations suggest that Septin4 as an essential molecule contribute to the occurrence and development of human colon cancer and provide new technical approaches for targeted treatment of this disease.

Keywords: Septin4, BAX, Colon Cancer, apoptosis