Targeting Galectin-1 Overcomes Paclitaxel Resistance in Esophageal Squamous Cell Carcinoma.

Autor:	Zhou L; Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.; China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.; Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, China., Tian J; Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.; China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.; Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, China., Wang K; Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, China., Ma Y; Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China., Chen X; China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.; Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, China., Luo H; Department of Radiation Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China., Lu B; Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.; China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.; Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, China., Wang N; Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.; China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.; Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, China., Wang P; College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, China., Liu X; Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.; China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.; Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, China., Zhao R; Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.; China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.; Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, China., Zhao S; China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.; Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, China.; Department of Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China., Wang J; China-US (Henan) Hormel Cancer Institute, Zhengzhou, China., Nie W; China-US (Henan) Hormel Cancer Institute, Zhengzhou, China., Ge H; Department of Radiation Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China., Liu W; Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.; China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.; Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, China., Gu T; Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.; China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.; Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, China., Liu K; Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.; China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.; Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, China.; The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, China.; State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, China., Lee MH; Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.; China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.; Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, China.; The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, China.; State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, China., Li X; Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.; China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.; Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, China.; The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, China.; State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, China., Dong Z; Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.; China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.; Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, China.; The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, China.; State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, China.
Jazyk:	angličtina
Zdroj:	Cancer research [Cancer Res] 2024 Nov 15; Vol. 84 (22), pp. 3894-3908.
DOI:	10.1158/0008-5472.CAN-23-2241
Abstrakt:	Resistance to paclitaxel poses a major obstacle in esophageal squamous cell carcinoma (ESCC) treatment. A better understanding of the mechanisms underlying paclitaxel resistance could help identify prognostic biomarkers and improved therapeutic strategies. In this study, we established a patient-derived xenograft model of acquired paclitaxel resistance and used RNA sequencing to identify galectin-1, encoded by LGALS1, as a key mediator of resistance. Integrative analysis of clinical data and physiological studies indicated that serum galectin-1 levels were elevated in resistant patients and correlated with treatment outcomes before and during taxane therapy. Importantly, exposing cells to serum from resistant patients resulted in increased paclitaxel resistance compared to serum from sensitive patients, which was closely associated with galectin-1 concentrations in the serum. The specific clearance of galectin-1 from resistant patient serum significantly restored paclitaxel sensitivity, and inhibiting galectin-1, through knockdown or the pharmacologic inhibitor OTX008, increased sensitivity to paclitaxel. Galectin-1 inhibition reduced the activity of β-catenin, thereby inhibiting stem cell properties induced by the Wnt/β-catenin pathway. Furthermore, galectin-1 regulated MDR1 transcription through increased nuclear accumulation of β-catenin, thus increasing resistance to paclitaxel. Combining OTX008 with clinical taxane formulations effectively reversed paclitaxel resistance in vitro and in vivo. Elevated galectin-1 levels thus serve as an indicator of response to paclitaxel therapy in ESCC, offering a therapeutic intervention strategy to overcome drug resistance. Significance: Galectin-1 is a key mediator of paclitaxel resistance in esophageal squamous cell carcinoma that can be targeted to improve taxane efficacy, suggesting broad therapeutic potential for treating various cancer types. (©2024 American Association for Cancer Research.)
Databáze:	MEDLINE
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