2. Academic Validation
  3. Fungal antitumor protein D1 is internalized via endocytosis and inhibits non-small cell lung cancer proliferation through MAPK signaling pathway

Fungal antitumor protein D1 is internalized via endocytosis and inhibits non-small cell lung cancer proliferation through MAPK signaling pathway

  • Int J Biol Macromol. 2022 Dec 12;227:45-57. doi: 10.1016/j.ijbiomac.2022.12.061.
Min-Hui Zhang 1,  Jack Ho Wong 2,  Fang Liu 3,  Tzi Bun Ng 4,  Zhao-Kun Liu 5
Affiliations

Affiliations

  • 1 Department of Microbiology, The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China.
  • 2 School of Health Sciences, Caritas Institute of Higher Education, Hong Kong, China.
  • 3 Department of Microbiology, The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China. Electronic address: [email protected].
  • 4 School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China. Electronic address: [email protected].
  • 5 Research Institute of Public Health, School of Medicine, Nankai University, Tianjin 300071, China. Electronic address: [email protected].
PMID: 36521713 DOI: 10.1016/j.ijbiomac.2022.12.061
Abstract

Lung Cancer has the highest mortality among cancer-related deaths worldwide. Among lung cancers, non-small cell lung Cancer (NSCLC) is the most common histological type. In the previous research, we isolated a protein (D1) from Boletus bicolor that inhibits the proliferation of NSCLC cell lines. In this study, we elucidated the internalization mechanism and antitumor mechanism of protein D1 in A549 cells. Protein D1 has a strong inhibitory effect on A549 cells. It binds to secretory carrier membrane protein 3 on the A549 cell membrane and enters A549 cells by clathrin-mediated endocytosis. In vitro, protein D1 activates mitogen-activated protein kinase (MAPK) signaling pathway. JNK and p38MAPK are the biological targets for protein D1. In vivo, protein D1 inhibits the tumor growth of NSCLC xenografts by inducing Apoptosis and inhibiting cell proliferation. Protein D1 alters the expression of genes related to Apoptosis, cell cycle, and MAPK signaling pathway in tumor cells.

Keywords

Fungal antitumor protein D1; Internalization mechanism; MAPK signaling pathway; NSCLC.

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