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GMI, a Ganoderma microsporum protein, abolishes focal adhesion network to reduce cell migration and metastasis of lung cancer.
Lo, Hung-Chih; Hua, Wei-Jyun; Yeh, Hsin; Lin, Zhi-Hu; Huang, Li-Chen; Ciou, Yi-Ru; Ruan, Runcheng; Lin, Kai-Fan; Tseng, Ai-Jung; Wu, Alexander T H; Hsu, Wei-Hung; Chao, Chi-Hong; Lin, Tung-Yi.
Afiliación
  • Lo HC; Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei, Taiwan.
  • Hua WJ; Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei, Taiwan.
  • Yeh H; Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • Lin ZH; Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • Huang LC; Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • Ciou YR; Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • Ruan R; Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • Lin KF; Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • Tseng AJ; Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • Wu ATH; The Ph.D. Program for Translational Medicine, College of Medical Science & Technology, Taipei Medical University, Taipei Taiwan.
  • Hsu WH; Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; LO-Sheng Hospital Ministry of Health and Welfare, Taipei, Taiwan; School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.
  • Chao CH; Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan; Center For Intelligent Drug Systems and Smart Bio-devices (IDS(2)B), National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
  • Lin TY; Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei, Taiwan; Biomedical Industry Ph.D. Program, National Yang Ming Chiao Tung University, Taipei, Taiwan. Elect
Life Sci ; 335: 122255, 2023 Dec 15.
Article en En | MEDLINE | ID: mdl-37967792
BACKGROUND: Cancer metastasis is a major cause of cancer-related deaths, emphasizing the urgent need for effective therapies. Although it has been shown that GMI, a fungal protein from Ganoderma microsporum, could suppress primary tumor growth in a wide spectrum of cancer types, it is still unclear whether GMI exhibits anti-metastasis properties, particularly in lung cancers. Further investigation is needed. AIMS AND OBJECTIVES: The objective of this study is to investigate the potential inhibitory effects of GMI on lung cancer metastasis in vivo. Utilizing systematic and comprehensive approaches, our research aims to elucidate the underlying molecular mechanisms responsible for the anti-metastatic effects. MATERIALS AND METHODS: In vitro migration and cell adhesion assays addressed the epithelial-to-mesenchymal transition (EMT)-related phenotype. Proteomic and bioinformatic analyses identified the GMI-regulated proteins and cellular responses. GMI-treated LLC1-bearing mice were analyzed using IVIS Spectrum to assess the anti-metastatic effect. KEY FINDINGS: GMI inhibits EMT as well as cell migration. GMI disrupts cell adhesion and downregulates integrin, resulting in inhibition of phosphorylated FAK. GMI induces macropinocytosis and lysosome-mediated degradation of integrin αv, α5, α6 and ß1. GMI downregulates Slug via inhibition of FAK activity, which in turn enhances expressions of epithelial-related markers and decreases cell mobility. Mechanistically, GMI-induced FAK inhibition engenders MDM2 expression and enhances MDM2/p21/Slug complex formation, leading to Slug degradation. GMI treatment reduces the metastatic pulmonary lesion and prolongs the survival of LLC1-bearing mice. SIGNIFICANCE: Our findings highlight GMI as a promising therapeutic candidate for metastatic lung cancers, offering potential avenues for further research and drug development.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pulmonares Límite: Animals Idioma: En Revista: Life Sci Año: 2023 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Países Bajos
Texto completo
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pulmonares Límite: Animals Idioma: En Revista: Life Sci Año: 2023 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Países Bajos