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Galectin-1-mediated MET/AXL signaling enhances sorafenib resistance in hepatocellular carcinoma by escaping ferroptosis.
Hsu, Tung-Wei; Su, Yen-Hao; Chen, Hsin-An; Liao, Po-Hsiang; Shen, Shih Chiang; Tsai, Kuei-Yen; Wang, Tzu-Hsuan; Chen, Alvin; Huang, Chih-Yang; Shibu, Marthandam Asokan; Wang, Wan-Yu; Shen, Shing-Chuan.
Afiliación
  • Hsu TW; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
  • Su YH; Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan.
  • Chen HA; Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan.
  • Liao PH; TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei 11031, Taiwan.
  • Shen SC; Division of General Surgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
  • Tsai KY; TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei 11031, Taiwan.
  • Wang TH; Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan.
  • Chen A; TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei 11031, Taiwan.
  • Huang CY; Division of General Surgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
  • Shibu MA; TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei 11031, Taiwan.
  • Wang WY; Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan.
  • Shen SC; Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan.
Aging (Albany NY) ; 15(13): 6503-6525, 2023 07 11.
Article en En | MEDLINE | ID: mdl-37433225
Sorafenib, a small-molecule inhibitor targeting several tyrosine kinase pathways, is the standard treatment for advanced hepatocellular carcinoma (HCC). However, not all patients with HCC respond well to sorafenib, and 30% of patients develop resistance to sorafenib after short-term treatment. Galectin-1 modulates cell-cell and cell-matrix interactions and plays a crucial role in HCC progression. However, whether Galectin-1 regulates receptor tyrosine kinases by sensitizing HCC to sorafenib remains unclear. Herein, we established a sorafenib-resistant HCC cell line (Huh-7/SR) and determined that Galectin-1 expression was significantly higher in Huh-7/SR cells than in parent cells. Galectin-1 knockdown reduced sorafenib resistance in Huh-7/SR cells, whereas Galectin-1 overexpression in Huh-7 cells increased sorafenib resistance. Galectin-1 regulated ferroptosis by inhibiting excessive lipid peroxidation, protecting sorafenib-resistant HCC cells from sorafenib-mediated ferroptosis. Galectin-1 expression was positively correlated with poor prognostic outcomes for HCC patients. Galectin-1 overexpression promoted the phosphorylation of AXL receptor tyrosine kinase (AXL) and MET proto-oncogene, receptor tyrosine kinase (MET) signaling, which increased sorafenib resistance. MET and AXL were highly expressed in patients with HCC, and AXL expression was positively correlated with Galectin-1 expression. These findings indicate that Galectin-1 regulates sorafenib resistance in HCC cells through AXL and MET signaling. Consequently, Galectin-1 is a promising therapeutic target for reducing sorafenib resistance and sorafenib-mediated ferroptosis in patients with HCC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma Hepatocelular / Ferroptosis / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Aging (Albany NY) Asunto de la revista: GERIATRIA Año: 2023 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma Hepatocelular / Ferroptosis / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Aging (Albany NY) Asunto de la revista: GERIATRIA Año: 2023 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos