TAOK3 Facilitates Esophageal Squamous Cell Carcinoma Progression and Cisplatin Resistance Through Augmenting Autophagy Mediated by IRGM

Author:

Sun Mingchuang1,Li Zhaoxing1,Wang Xiaoyuan1,Zhao Meirong2,Chu Yuan1,Zhang Zehua1,Fang Kang1,Zhao Ziying1,Feng Anqi1,Leng Zhuyun1,Shi Jianing1,Zhang Li3,Chen Tao1,Xu Meidong1ORCID

Affiliation:

1. Endoscopy Center Department of Gastroenterology Shanghai East Hospital School of Medicine Tongji University Shanghai 200120 China

2. Shanghai East Hospital Jinzhou Medical University Liaoning 121001 China

3. Department of Pathology Shanghai East Hospital School of Medicine Tongji University Shanghai 200120 China

Abstract

AbstractEsophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers because of its robust aggressive phenotype and chemoresistance. TAO kinase belongs to mitogen‐activated protein kinases, which mediate drug resistance in multiple cancers. However, the role of TAO kinase in ESCC progression and chemoresistance has never been explored. Here, it is reported that TAOK3 augments cell autophagy and further promotes ESCC progression and chemoresistance. Mechanistically, TAOK3 phosphorylates KMT2C at S4588 and strengthens the interaction between KMT2C and ETV5. Consequently, the nuclear translocation of KMT2C is increased, and the transcription of autophagy‐relevant gene IRGM is further upregulated. Additionally, the inhibitor SBI‐581 can significantly suppress cell autophagy mediated by TAOK3 and synergizes with cisplatin to treat ESCC in vitro and in vivo.

Funder

National Natural Science Foundation of China

Publisher

Wiley

Subject

General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)

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