Review Article

Kelch-like proteins in the gastrointestinal tumors

An-bo Fu1,2,3, Sen-feng Xiang1, Qiao-jun He1,4, Mei-dan Ying1,4
1 Institute of Pharmacology and Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
2 Institute of Gastroenterology, Zhejiang University, Hangzhou 310002, China
3 Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310002, China
4 Cancer Center, Zhejiang University, Hangzhou 310058, China
Correspondence to: Sen-feng Xiang:, Qiao-jun He:, Mei-dan Ying:,
DOI: 10.1038/s41401-022-01007-0
Received: 16 April 2022
Accepted: 22 September 2022
Advance online: 20 October 2022


Gastrointestinal tumors have become a worldwide health problem with high morbidity and poor clinical outcomes. Chemotherapy and surgery, the main treatment methods, are still far from meeting the treatment needs of patients, and targeted therapy is in urgent need of development. Recently, emerging evidence suggests that kelch-like (KLHL) proteins play essential roles in maintaining proteostasis and are involved in the progression of various cancers, functioning as adaptors in the E3 ligase complex and promoting the specific degradation of substrates. Therefore, KLHL proteins should be taken into consideration for targeted therapy strategy discovery. This review summarizes the current knowledge of KLHL proteins in gastrointestinal tumors and discusses the potential of KLHL proteins as potential drug targets and prognostic biomarkers.
Keywords: gastrointestinal tumors; KLHL; therapeutic target; prognostic biomarker; substrate

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