Bufalin inhibits the proliferation of lung cancer cells by suppressing Hippo-YAP pathway

Zijun Qian; Xiaoting Tian; Yayou Miao; Xin Xu; Xuehua Cheng; Mengyi Wu; Yongchun Yu

doi:10.1016/j.cellsig.2023.110746

Bufalin inhibits the proliferation of lung cancer cells by suppressing Hippo-YAP pathway

Cell Signal. 2023 Sep:109:110746. doi: 10.1016/j.cellsig.2023.110746. Epub 2023 Jun 5.

Authors

Zijun Qian¹, Xiaoting Tian², Yayou Miao², Xin Xu², Xuehua Cheng³, Mengyi Wu⁴, Yongchun Yu⁵

Affiliations

¹ Department of Clinical Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China.
² Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
³ Department of TCM Geriatrics, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China.
⁴ Shanghai University of Traditional Chinese Medicine, 201203, China.
⁵ Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China. Electronic address: yongchunyu2022@126.com.

PMID: 37286119
DOI: 10.1016/j.cellsig.2023.110746

Abstract

Lung cancer has high morbidity and mortality. This study demonstrated that Bufalin inhibits the proliferation of lung cancer cells in vivo / in vitro by suppressing Hippo-YAP pathway. Here, we found that Bufalin promoted the binding of LATS and YAP to elevate the level of YAP phosphorylation. Phosphorylated YAP could not successfully enter the nucleus to activate the expression of downstream proliferation-related target genes Cyr61 and CTGF, whereas the YAP retained in the cytoplasm further bound to β-TrCP and underwent ubiquitination and degradation. This study verified the key role of YAP in stimulating the proliferation of lung cancer and revealed the anticancer target of Bufalin. Therefore, this study provides a theoretical basis for the anticancer effect of Bufalin, and suggests that Bufalin can be a potential anticancer drug.

Keywords: Bufalin; Hippo; Lung cancer; YAP.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / metabolism
Bufanolides
Cell Proliferation / genetics
Humans
Lung Neoplasms* / drug therapy
Protein Serine-Threonine Kinases* / metabolism
Transcription Factors / metabolism

Substances

Protein Serine-Threonine Kinases
Adaptor Proteins, Signal Transducing
Transcription Factors
bufalin
Bufanolides